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Intracoronary C5a in swine decreases coronary blood flow and regional myocardial segment shortening, responses mediated by thromboxane (Tx) A2-induced coronary vasoconstriction and intramyocardial trapping of granulocytes (PMNs). We sought to determine the origin of TxA2 and to investigate the role of CD18-dependent PMN function by utilizing an anti-CD18 monoclonal antibody, IB4. Isolated C5a-stimulated PMNs or platelets did not produce TxB2. However, together, C5a-stimulated PMNs and platelets produced TxB2. IB4 bound porcine PMN surface CD18 and blocked C5a-induced PMN functions. In vivo, IB4 loading (2 mg/kg) transiently decreased arterial blood pressure and circulating platelet counts in six of nine animals (390 +/- 31 vs. 176 +/- 41 X 10(6)/ml, control vs. IB4; P < 0.002) and significantly ameliorated C5a-induced decreases in coronary venous PMN count (-4.1 +/- 0.6 vs. -1.4 +/- 0.8 X 10(6) cells/ml), coronary artery blood flow (-10 +/- 1 vs. -4 +/- 1 ml/min), and segment shortening (-15 +/- 2 vs. -8 +/- 2%, C5a vs. C5a + IB4). We conclude that 1) production of TxB2 in response to C5a is mediated by a PMN-platelet interaction, 2) IB4 functionally blocks CD18 on porcine PMNs, and 3) C5a-induced myocardial PMN extraction is mediated, in part, by a CD18-dependent mechanism. These results suggest that PMN-platelet interactions and CD18-dependent PMN extraction are important in C5a-induced myocardial ischemia.

Small-vessel vasospasm has been speculated upon as a possible cause of chest pain in patients with normal-appearing coronary angiograms. In this report, a patient who experienced typical chest pain during acetylcholine testing, which caused ST segment elevation without epicardial coronary spasm, is presented. This finding suggests that small-vessel vasospasm may be involved in the induction of myocardial ischemia in patients with normal epicardial coronary arteries.

A 53-year-old woman was admitted to the hospital for chest pain with headache, nausea and vomiting, two and a half hours after an intramuscular injection of 6 x 10(6) units of IFN (interferon) alpha 2a, in the 11th week of IFN treatment for chronic hepatitis C. The electrocardiogram (ECG) showed ST depression and T inversion in leads II, III, aVF and V3-V6, as commonly seen in myocardial ischemia. However, emergency coronary angiography (CAG) did not show stenosis or spasms clearly, serum CPK was always within the normal limits, Tc-99m PYP scintigraphy and T1-201 scintigraphy did not show any abnormal uptake or defect, and the echocardiogram did not show any abnormality. She recovered from chest pain and the ischemia-like changes seen on the ECG, after IFN treatment was stopped, and she rested for 7 days from this treatment and other treatment using nitrites and a calcium-antagonist. After recovery, the ECG during exercise and hyperventilation showed changes similar to those seen on admission. From these findings, this case was considered to be precipitated by spasms of coronary microvessels, which were not noticeable in CAG. The cause was thought to be complicated by IFN treatment, because this episode appeared after IFN injection, and improved after stopping IFN treatment.

Isoflurane may precipitate ischemia in patients with coronary artery disease, presumably via "coronary steal." We sought to examine whether myocardial ischemia is more common in patients with coronary artery disease receiving isoflurane (0.7%) than in a control group receiving enflurane (0.9%). Thirty-eight patients scheduled for coronary artery bypass surgery were randomly assigned one anesthetic and monitored for ischemia. All patients had ejection fractions of at least 45%. Extraneous causes of ischemia were controlled as much as possible: arterial blood pressure was maintained within 20% of baseline (primarily with phenylephrine), heart rate was maintained below 80 bpm, effects from endotracheal intubation were monitored, and measurements were made before incision. Electrocardiogram, transthoracic echocardiography, and coronary sinus lactate measurement were used to detect ischemia. Measurements were made after insertion of vascular catheters, after intubation, and after 20 min of breathing the inhaled anesthetic. During the awake period and after induction of anesthesia with fentanyl (25 micrograms/kg), there was no significant difference detected between the two groups in incidence of ischemia: 20% in the enflurane group and 22% in the isoflurane group (P = 0.38). After 20 min of receiving the inhaled anesthetic, the incidence of ischemia in the isoflurane group increased to 50%, whereas the incidence in the enflurane group was unchanged at 20% (P = 0.02). These results show that, even with strict control of hemodynamics, isoflurane is associated with more myocardial ischemia than is enflurane.

5-Fluorouracil (5-FU) is a commonly employed chemotherapeutic agent. Among the various toxicities associated with 5-FU, cardiovascular toxicity, consisting principally of acute myocardial ischemia and/or myocardial infarction, has been reported in up to 8.5% of patients treated with this drug. While 5-FU-induced coronary vasospasm has been considered as a potential basis for such clinical toxicity, this hypothesis remains unsubstantiated by laboratory investigation. Accordingly, the present study was designed to investigate the hypothesis that 5-FU induces reversible vasoconstriction of vascular smooth muscle and to study the cellular mechanisms of such vasomotor alterations. To investigate the effects of 5-FU on the vasoreactivity of vascular smooth muscle, 479 exposures were performed in 105 rings of aorta freshly isolated from 23 New Zealand white rabbits. Vasoconstriction was documented in 20 of 86 (23%) rings exposed to 5-FU at 7 x 10(-5) M, 45 of 83 (54%) rings exposed to 5-FU at 7 x 10(-4) M, and 41 of 49 (84%) rings exposed to 5-FU at 7 x 10(-3) M. In each case, 5-FU-induced vasoconstriction was endothelium independent. Pretreatment of rings with 10(-9) M staurosporine, a protein kinase C (PK-C) inhibitor, reduced 5-FU-induced vasoconstriction from 25.0 +/- 6.5 to 2.5 +/- 1.7 mg; staurosporine at a concentration of 10(-8) M abolished 5-FU-induced vasoconstriction. Pretreatment of rings with 10(-7) M phorbol-12,13-dibutyrate, an activator of PK-C, increased the magnitude of 5-FU-induced vasoconstriction 23-fold, from 49.7 +/- 11.1 mg before to 1163.6 +/- 276.4 mg after phorbol-12,13-dibutyrate (P = 0.0002). Neomycin, an inhibitor of phosphoinositide turnover, did not alter the magnitude of 5-FU-induced vasoconstriction. Membrane receptor blockers, including the alpha-adrenergic receptor blocker phentolamine, the beta-adrenergic receptor blocker propranolol, the H1 receptor inhibitor diphenhydramine, the H2 receptor inhibitor cimetidine, the Ca2+ channel blockers verapamil and diltiazem, and the cyclooxygenase inhibitor indomethacin all failed to alter the magnitude of 5-FU-induced vasoconstriction. Furthermore, the 5-FU-related compounds uracil and floxuridine did not produce vasoconstriction. Finally, 5-FU-induced vasoconstriction was abolished by nitroglycerin. These results indicate that (a) 5-FU causes direct, endothelium-independent vasoconstriction of vascular smooth muscle in vitro, (b) this vasomotor response involves activation of PK-C, and (c) this response is independent of vasoactive cell membrane receptors, phosphoinositide turnover, or activation of the cyclooxygenase pathway.(ABSTRACT TRUNCATED AT 400 WORDS)

We describe the case of a 39-year-old woman, heavy smoker, who received 500 micrograms i.m. of Sulprostone, a synthetic PGE2-derivative, to induce pregnancy termination. Sulprostone is usually administered either to cause abortion in preparation of an instrumental operation or to induce delivery after the intrauterine death of the fetus. This drug has a dilating effect on the cervix uteri and stimulates the uterus muscles. After about fifteen minutes the patient experienced a constrictive chest pain which progressively worsened and spread to the upper limbs. The pain disappeared for a short period and then recurred with greater intensity, accompanied by bradycardia and hypotension. The ECG showed sinus bradycardia, second- and third-degree atrioventricular block, S-T segment elevation in the inferior leads and reciprocal depression in the anterior leads. Intravenous nitroglycerin therapy induced a rapid reduction of the clinical symptoms and changes in the ECG. There was no increase in cardiac enzymes. The exercise test, the cold pressor test and the ECO-dipyridamole test were negative. The patient refused to undergo the ergonovine test and coronary angiography. We hypothesize that the Sulprostone either had a dipyridamole-like effect or that it induced a paradoxal coronary spasm.

Objective: The calcium antagonist nisoldipine has recently been reported to induce rather than to attenuate ischaemia in some patients with stable angina. The aim of the study was to investigate the mechanisms underlying this proischaemic effect., Methods: In 20 anaesthetised dogs systemic haemodynamic variables, regional myocardial blood flow (coloured microspheres), and systolic wall thickening (sonomicrometry) were measured during control conditions and following severe stenosis on the left circumflex coronary artery, before and after intravenous administration of equihypotensive doses of either nisoldipine (group I, n = 10) or dipyridamole (group II, n = 10). Finally, measurements were performed while the drug induced decreases in mean aortic pressure--18 (SD 6) mmHg in group I and 14(6) mm Hg in group II--were reversed by inflation of an intra-aortic balloon., Results: The stenosis decreased posterior wall thickening to 50% of control, and posterior subendocardial blood flow from 1.48(0.27) to 0.61(0.19) ml.min-1.g-1 in group I and from 1.49(0.23) to 0.62(0.18) ml.min-1.g-1 in group II. Subendocardial blood flow was further decreased after administration of either nisoldipine [0.37(0.20) ml.min-1.g-1, p < 0.05 v stenosis] or dipyridamole [0.22(0.11) ml.min-1.g-1, p < 0.05 v stenosis]. Regional myocardial blood flow in the anterior region was increased. The drug induced reduction of subendocardial blood flow decreased posterior wall thickening further from 9.3(2.1) to 6.2(3.9)% (p < 0.05 v stenosis, group I) and from 9.1(1.7) to 4.3(2.4)% (p < 0.05 v stenosis, group II). When the drug induced decrease in aortic pressure was reversed, subendocardial blood flow again increased in group I [0.63(0.19) ml.min-1.g-1, p < 0.05 v stenosis and nisoldipine] whereas in group II it remained decreased [0.40(0.29) ml.min-1.g-1, NS v stenosis and dipyridamole]. There was restoration of posterior wall thickening in group I [10.4(3.8)%, p < 0.05 v stenosis and nisoldipine], but not in group II [5.2(3.5)%, NS v stenosis and dipyridamole]., Conclusions: Nisoldipine and dipyridamole decrease subendocardial blood flow and contractile function distal to a severe stenosis when aortic pressure is decreased. No aggravation of ischaemia by nisoldipine is seen when hypotension is prevented. In contrast, dipyridamole in the absence of hypotension still induces a redistribution of flow at the expense of the ischaemic region.

We investigated the effects of clentiazem, a 1,5-benzothiazepine calcium antagonist, on epinephrine-induced cardiomyopathy in rats. With 2-week chronic epinephrine infusion, 16 of 30 rats died within 4 days, and severe ischemic lesions and fibrosis of the left ventricles were observed. In epinephrine-treated rats, left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced, but responses to calcium were normal or enhanced compared to controls. Left ventricular alpha and beta adrenoceptor densities were also reduced compared to controls. Treatment with clentiazem prevented epinephrine-induced death (P < .05), and attenuated the ventricular ischemic lesions and fibrosis, in a dose-dependent manner. Left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced compared to controls in groups treated with clentiazem alone, but combined with epinephrine, clentiazem restored left atrial responses and enhanced left ventricular papillary responses to isoproterenol. On the other hand clentiazem did not prevent epinephrine-induced down-regulation of alpha and beta adrenoceptors. Interestingly, clentiazem, infused alone, resulted in decreased adrenergic receptor densities in the left ventricle. Clentiazem also did not prevent the enhanced responses to calcium seen in the epinephrine-treated animals, although the high dose of clentiazem partially attenuated the maximal response to calcium compared to epinephrine-treated animals. In conclusion, clentiazem attenuated epinephrine-induced cardiac injury, possibly through its effect on the adrenergic pathway.

We sought to determine the influence of nitrous oxide on the compromised heart during propofol anesthesia. This study investigated the cardiovascular effects of the combination propofol and nitrous oxide (N2O). Seven beagles were monitored to measure global and regional left ventricular function. Recordings both before and after critical constriction (CC) of the left anterior descending coronary artery (LAD) were performed after propofol, 300 micrograms.kg-1.min-1, and 10 min after exposure to and discontinuation of 67% N2O. Data were analyzed with ANOVA for repeated measures at 95% confidence level. In the absence of CC, N2O caused moderate, reversible hemodynamic depression (LVdP/dtmax, -13.8%; cardiac output, -17.2%; LAD coronary blood flow, -10.9%) and no regional dysfunction. After CC global hemodynamic depression was of similar magnitude (LVdP/dtmax, -19.9%; cardiac output, -9.2%; stroke volume, -9.2%) but did not recover completely. Systolic shortening in the compromised area decreased (-30.3%) and postsystolic shortening developed to represent 20.3% of total shortening. Despite only moderate hemodynamic depression, 67% N2O causes substantial regional dysfunction in compromised myocardium when added to propofol.

This prospective study examined whether neonates of pregnant women who used cocaine during pregnancy are at a risk for the development of transient myocardial ischemia and altered autonomic function, as in adults. We studied 21 of 35 infants with a history of prenatal exposure to cocaine. The ST segment changes and heart rate variability were evaluated from three-channel Holter monitors within 48 hours of birth. The data were compared with those on 20 control infants with similar birth weight, gestational age, and postnatal age. Six infants (29%) who were exposed to cocaine in utero had transient ST segment elevation, versus only one infant (5%) from the control group (odds ratio = 7.6; 95% confidence interval, 1.14, 50.64). Heart rates, results of total power and low-frequency power spectral analyses for heart rate variability, and arrhythmias were not significantly different in the two groups. However, a lower ratio of low-to high-frequency power reflected increased vagal activity in cocaine-exposed infants. We conclude that cocaine use in pregnant mothers is associated with transient ST segment abnormalities in their infants. These abnormalities are consistent with transient myocardial ischemia.

The therapeutic potency of 5,6,7,8-tetrahydroneopterin (NPH4) was investigated in ischemic paw edema, Adriamycin (ADR)-induced cardiotoxicity, and endotoxin [lipopolysaccharide (LPS)]- and carbon tetrachloride (CCl4)-induced hepatotoxicity in mice. Ischemic paw edema was completely suppressed by pre-administration of NPH4. ADR-induced cardiotoxicity and LPS-induced hepatotoxicity were significantly decreased by post-administration of NPH4. Furthermore, NPH4 ameliorated CCl4-induced hepatotoxicity. These results suggest that NPH4 may be useful for the treatment of free radical, especially superoxide radical, -related tissue injury.

Ornipressin (OR), a synthetic derivative of natural vasopressin, is widely used in combination with local anaesthetics in order to reduce surgical bleeding and systemic absorption of the local anaesthetic. As shown previously in experimental studies, OR causes severe coronary vasoconstriction. The myocardial oxygen balance is compromised by an increase in myocardial oxygen demand due to hypertension and impaired oxygen delivery following coronary vasoconstriction. We describe the case of a 19-year-old male who was admitted to the hospital for elective tonsillectomy. There was no evidence of systemic or cardiovascular disease (ASA I). Following the induction of anaesthesia with thiopentone 4 mg/kg and ventilation with N2O/O2 (FiO2:0.25), vecuronium was administered to facilitate orotracheal intubation. Anaesthesia was maintained with N2O/O2 (FiO2:0.33) and 2 MAC isoflurane. After reaching an anaesthetic steady state with stable haemodynamic conditions, peritonsillar infiltration with a prilocaine solution containing a total of 0.8 IU OR (0.1 IU/ml) produced marked tachycardia and hypertension. Concomitantly, distinct ST-segment-depression was observed in a lead II ECG. Hypertension and tachycardia occurred within 3 min after the local infiltration with prilocaine/OR. Maximum ST-segment depression and haemodynamic changes were recorded 11 min after infiltration, with an increase in heart rate from 58 to 136 min and a rise in blood pressure from 115/50 to 217/130 mmHg. Considering experimental results, the ECG changes in this case show clear evidence that even in healthy humans OR-induced systemic haemodynamic changes may be complicated by severe myocardial ischaemia due to coronary vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

A patient with vasospastic angina who developed myocardial ischemia following ethanol ingestion but not after exercise was described. Myocardial ischemia was evidenced by electrocardiograms (ECGs) and thallium-201 scintigrams. The blood acetaldehyde level after ethanol ingestion was abnormally high. The time course and severity of myocardial ischemia coincided with those of the blood ethanol and acetaldehyde level. Coronary arteriography showed ergonovine maleate-induced coronary vasospasm at the left anterior descending coronary artery. ECG changes similar to those induced by ethanol ingestion were observed at the same time. These findings suggest that the high blood acetaldehyde level might be responsible for the development of coronary vasospasm and myocardial ischemia in this patient.

Activated complement component C5a causes myocardial ischemia mediated by thromboxane (Tx) A2 and leukotrienes C4/D4. Blood cells are not involved in either the mediator release or the myocardial effects of C5a, suggesting that a C5a-sensitive, cardiac resident inflammatory cell is responsible. The goals of this study were to determine whether 1) cardiac mast cell activation accompanies the C5a response, 2) inhibition of mast cell degranulation inhibits the response, and 3) histamine release plays a role in the C5a-induced myocardial ischemia. The left anterior descending coronary artery (LAD) of open-chest pigs (n = 13) was perfused with arterial blood at constant pressure (95 mmHg). Coronary blood flow (CBF) was measured (in-line flowmeter) and regional function [percent segment shortening (%SS)] determined with sonomicrometry. A coronary vein was cannulated for measurement of plasma TxB2 and histamine (a marker of mast cell degranulation). Intracoronary C5a (500 ng) decreased coronary blood flow (45% of preinfusion levels) and LAD %SS (65% of preinfusion) and was accompanied by increases in coronary venous TxB2 (delta 63.3 ng/ml) and histamine (delta 200 nM). Mast cell inhibition with lodoxamide (2 mg/kg iv, n = 8) attenuated the C5a-induced fall in CBF (14 vs. 53% decrease, P < 0.01) and %SS (10 vs. 38% decrease, P < 0.01) and also reduced the C5a-induced increase in both coronary venous histamine (delta 26 vs. 278 nM, P < 0.05) and TxB2 (delta 0.34 vs. 63.3 ng/ml, P < 0.01). However, histamine H1 (pyrilamine) and H2 (ranitidine) receptor blockade had no effect on the C5a-induced fall in CBF or LAD %SS.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocaine use has reached epidemic proportions in the United States. Patients may present having ingested cocaine for elective or emergent operative procedures. We report a case of acute myocardial ischemia in a young healthy male patient.

We report a case of myocardial ischemia induced by cocaine. The ischemia probably induced by coronary artery spasm was reversed by nitroglycerin and calcium blocking agents.

Background: Myocardial ischemia attributed to coronary steal may occur in some patients receiving pharmacological coronary vasodilation. ECG ST-segment depression is a marker of myocardial ischemia in these patients, but the factors determining the presence or absence of ischemia are not well known., Methods and Results: To examine the angiographic, hemodynamic, and scintigraphic determinants of adenosine-induced ischemic ST-segment depression in patients with coronary artery disease, we studied 65 consecutive patients (45 men and 20 women; mean age, 65 +/- 12 years) who showed reversible perfusion defects during adenosine (140 micrograms.kg-1.min-1 for 6 minutes) 201Tl single-photon emission computed tomography. Patients with prior myocardial infarction were excluded. Ischemic ST depression occurred in one third of the whole cohort (22 of 65 patients). The presence of coronary collateral vessels (p = 0.001), systolic blood pressure at baseline (p = 0.006), and adenosine-induced anginal chest pain (p = 0.011) were the only significant independent predictors of ischemic ST-segment depression by stepwise logistic regression analysis. Rate-pressure product at baseline, systolic blood pressure, heart rate, rate-pressure product, increase in heart rate, and rate-pressure product during adenosine infusion and maximal percent stenosis were variables also significantly related to ischemic ST depression by univariate analysis but were not predictive after the three primary variables were included in the regression model. Perfusion defect size, number of diseased vessels, and age did not correlate with ST-segment depression., Conclusions: The presence of collaterals, which may predispose to coronary collateral steal, is the most significant correlate of ischemic ST-segment depression during adenosine infusion. Systolic blood pressure at baseline, which may affect the myocardial oxygen supply/demand ratio and anginal chest pain induced by adenosine, are additional variables related to ischemic ST-segment depression during adenosine infusion.

Mice were injected ip DSPM 1 or 3 mg.kg-1 3 h prior to a subcutaneous injection of isoproterenol (Iso) 20 mg.kg-1 once daily for 2 d. Iso induced reductions of Se-glutathione peroxidase (Se-GSH-PX), superoxide dismutase (SOD) activities, and an increase of malondialdehyde (MDA) content in myocardium. DSPM 1 or 3 mg.kg-1 significantly abated reduction of Se-GSH-PX activity and decreased MDA production and DSPM 3 mg.kg-1 also abated reduction of SOD activity in the hearts from Iso-treated mice. The changes of above indices were in accordance with those of myocardial ultrastructure and creatine phosphokinase (CPK) concentration in serum. The results indicate that DSPM has a protective effect on myocardial ischemic injury probably by inhibiting oxygen free radicals and subsequent lipid peroxidation.

Examinations are performed on 120 workers from the plant for nitrogen and 253 workers from the plant for phosphorous fertilizers. For comparison is used a control group of 103 persons having no professional contact with chemical noxa. The measuring of the arterial pressure and assessment of the arterial hypertension rate is performed after the standardised method of the World Health Organization (1984). The probability of ischemic disease of the heart is determined on the basis of the electrocardiographic changes (Minnesota code) and the data of the questionnaire of G. A. Rose (WHO, 1984). The results point out, that the arterial hypertension incidence and that of the ischemic disease of the heart in the exposed workers in both plants is insignificantly higher than that of the controls. There is no effect of the specialized length of service on the dissemination of the registered cardio-vascular diseases. The data of the carried out investigation show no presence of heightened risk of arterial hypertension and ischemic heart disease in workers from the nitrogen and phosphorous fertilizers production.

An increase in frequency of heart contractions, changes in the bioelectrical heart activity and decrease of the force-pump heart function are observed in the rabbits with model chronic ischemic heart disease lipid metabolism in significantly changed the concentration of cholesterol in the right ventricle myocardium as well as the concentrations of unsaturated lipid acids in the heart tissues increase, while the content of saturated lipid acids and antioxidant activity of plasma decrease. Bioenergetic processes change as follows: succinate-dehydrogenase and alpha-keto-glutarate-dehydrogenase activity decrease, while the concentrations of glycogen, lactic and pyruvic acids and lactate dehydrogenase activity in the heart tissues increase.

Cisplatin exerts an additional influence on myocardial ischemia induced by the cardiovascular effects of etoposide. Two cases of myocardial ischemia related to combination chemotherapy with methotrexate, etoposide and cisplatin are reported. While the major toxicity associated with systemic chemotherapy is hematologic, it is suggested that, in elderly patients with increased incidence of atherosclerotic disease, special attention be given to vascular complications of antineoplastic agents.

We have studied the incidence of new intraoperative myocardial ischaemia (IMI), myocardial infarction (MI) and cardiac death (CD) in 500 consecutive patients undergoing elective major non-cardiac vascular surgery. Patients were allocated randomly to receive either halothane (n = 226) or isoflurane (n = 274) as principal anaesthetic agent. Using real-time ST segment trend analysis (leads V5 and II) IMI (halothane 39%, isoflurane 38%), MI (halothane 1.3%, isoflurane 1.5%) and CD (halothane 0.4%, isoflurane 0.7%) did not differ significantly between the two groups. Twenty-three per cent of IMI episodes were related to haemodynamic disturbances, but unrelated to the type of surgery: 148 supra-aortic (IMI = 39%), 244 abdominal aortic (IMI = 41%) and 108 lower extremity revascularizations (IMI = 33%). We conclude that the choice of volatile anaesthetic agent does not influence cardiac morbidity or mortality in this type of patient.

Many clinical cases of cocaine-induced myocardial infarction have been reported in the literature. Of the reported cases, patients tend to be young (in the third decade of life), chronic abusers with myocardial infarction typically involving the anterior left ventricular wall. This case report demonstrates the usefulness of two-phase (symptomatic and asymptomatic) Tc-99m sestamibi myocardial imaging at rest for definitive diagnosis of cocaine-induced myocardial ischemia and infarction.

Isoproterenol (Iso, 20 mg.kg-1 x d-1 x 2 d) induced widespread and severe myocardial damages at ultrastructural level, decreased the myocardial Se-glutathione peroxidase (Se-GSH-Px) and superoxide dismutase (SOD) activities, increased the serum creatine phosphokinase (CPK) concentration and myocardial malondialdehyde (MDA) content. Phenytoin sodium (Phe) 15 or 30 mg.kg-1 ip pretreatment diminished the CPK release and MDA production, protected the Se-GSH-Px activity in the Iso-induced damage of mouse heart. The pretreatment with 30 mg.kg-1 abated the reduction of SOD activity. However, Phe 15 mg.kg-1 did not show such an effect. Phe (15 or 30 mg.kg-1) reduced the ultrastructural cardiotoxicity of Iso, and the membrane structure of ischemic myocardium was protected. The protective effects of verapamil pretreatment 3 mg.kg-1 ip were weaker than those of Phe on ultrastructural changes, but biochemical changes were similar to those of Phe. The results suggested that Phe possessed anti-lipid peroxidation and protective effects on ischemic myocardium.

It is apparent that a variety of vascular disorders have been reported after the administration of antineoplastic agents. However, it is not clear whether all of these entities are related to cytotoxic drugs, the malignancy itself, or some other unrelated factor. Nonetheless, there does appear to be a cause-effect relationship between cisplatin, bleomycin, velban chemotherapy, and Raynaud's phenomenon. In addition, painful acral erythema may occur in association with several drugs, especially protracted infusions of 5-fluorouracil and high-dose cytosine arabinoside. Mitomycin is the most common cause of the thrombotic microangiopathic syndrome, and in the majority of cases it is a lethal event. Unfortunately, HVOD is a major toxic effect of many preparatory bone marrow transplantation protocols and ways to prevent this potentially life-threatening complication should be avidly pursued. In this regard, pentoxifylline and low-dose heparin have recently been reported to be effective in preventing HVOD. Although recent reports have documented thromboses and thromboembolic events in patients with breast cancer treated with cytoxan, methotrexate, and 5-fluorouracil-based protocols, only one study had a no-treatment control arm. Future breast cancer studies should evaluate this problem prospectively. More studies are needed to help elucidate the pathogenesis of vascular toxicity associated with chemotherapy.

During induced myocardial ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is inhibited as anaerobic pathways predominate. Even following reperfusion, stunned myocardium uses oxygen and substrate inefficiently leading to poor functional recovery as less mechanical work is developed per oxygen utilized. Amino acids potentially can act as cardiac metabolic substrates during and after ischemia, utilizing the transamination of amino acids by the malate-aspartate shuttle to form high energy phosphates via the tricarboxylic acid cycle. We investigated if "preloading" hearts with a physiologic spectrum of amino acids could increase postischemic myocardial recovery. Isolated perfused rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia. Hearts received cardioplegia alone as controls or were "preloaded" with a 0.05% amino acid perfusion for 30 min prior to cardioplegic ischemia. Following reperfusion, analysis of functional recovery revealed that contractility and cardiac efficiency were improved with amino acids substrate preloading. The mechanism of this may be due to uptake of amino acids prior to ischemia, which are later utilized for internal reparative work during ischemia and external contractile work after ischemia.

Cocaine exerts a myriad of adverse cardiovascular effects which are dependent on the dose, rate of administration, and duration of use. The drug has two primary pharmacologic actions: it is a powerful sympathomimetic agent and a local anesthetic. The drug blocks the presynaptic reuptake of catecholamines resulting in the marked hormonal increase at the postsynaptic receptor sites. These effects, in turn, lower the threshold for coronary vasoconstriction and vasospasm, myocardial ischemia and infarction. In addition, the drug's multiple pharmacologic and electrophysiologic cardiovascular actions can promote arrhythmias, myocarditis, cardiomyopathy, as well as unmasking subclinical diseases. Long-term cocaine use can cause autonomic disturbances and alter catecholamine homeostasis: chronic cocaine addicts face serious cardiovascular sequelae from the drug's multiple adverse effects. It is important to assess the prevalence of cocaine-related cardiovascular diseases, to understand how the drug affects the autonomic nervous system, and to determine its long-term effects on the cardiovascular system.

This study evaluates the metabolic and physiologic effects of Verapamil on isolated, perfused rat hearts subjected to 1 hour of global ischemia. Hearts were perfused with a modified Krebs-Henseleit bicarbonate buffer with glucose. During working heart perfusion, mean aortic systolic pressure, heart rate, and aortic and coronary flows were measured. Cardiac output and minute work were calculated. In three groups of eight hearts, 60-minute global ischemia was followed by a 40-minute reperfusion to assess physiologic recovery. Three groups of 11 hearts were assayed for myocardial high-energy phosphates after ischemia. Untreated hearts recovered less than 15% of function and lost 50% of their high-energy phosphate stores. Hearts treated with Verapamil (2 microg/cc) prior to ischemia recovered greater than 85% of function and retained normal adenosine triphosphate (ATP) and 40% decreased creatine phosphate (CP) levels. The metabolic and physiologic effects of Verapamil lasted 20 minutes longer than potassium, possibly related to membrane binding and dissociation of Verapamil. Verapamil was shown to have cardioplegic and protective effects, both probably secondary to inhibition of calcium flux across the sarcolemmal membrane.