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Background: Cardiovascular diseases (CVDs) are considered a leading cause of death worldwide. Allelic variation in the CYP2C19 gene leads to a dysfunctional enzyme, and patients with this loss-of-function allele will have an impaired clopidogrel metabolism, which eventually results in major adverse cardiovascular events (MACE). Ischemic heart disease patients (n = 102) who underwent percutaneous cardiac intervention (PCI) followed by clopidogrel were enrolled in the present study., Methods: The genetic variations in the CYP2C19 gene were identified using the TaqMan chemistry-based qPCR technique. Patients were followed up for 1 year to monitor MACE, and the correlations between the allelic variations in CYP2C19 and MACE were recorded., Results: During the follow-up, we reported 64 patients without MACE (29 with unstable angina (UA), 8 with myocadiac infarction (MI), 1 patient with non-STEMI, and 1 patient with ischemic dilated cardiomyopathy (IDC)). Genotyping of CYP2C19 in the patients who underwent PCI and were treated with clopidogrel revealed that 50 patients (49%) were normal metabolizers for clopidogrel with genotype CYP2C19*1/*1 and 52 patients (51%) were abnormal metabolizers, with genotypes CYP2C19*1/*2 (n = 15), CYP2C19*1/*3 (n = 1), CYP2C19*1/*17 (n = 35), and CYP2C19*2/*17 (n = 1). Demographic data indicated that age and residency were significantly associated with abnormal clopidogrel metabolism. Moreover, diabetes, hypertension, and cigarette smoking were significantly associated with the abnormal metabolism of clopidogrel. These data shed light on the inter-ethnic variation in metabolizing clopidogrel based on the CYP2C19 allelic distribution., Conclusion: This study, along with other studies that address genotype variation of clopidogrel-metabolizing enzymes, might pave the way for further understanding of the pharmacogenetic background of CVD-related drugs., (© 2023. The Author(s).)

Introduction: Clinical trials of Compound danshen dripping pills (CDDP) indicated distinct improvement in patients with chronic stable angina. Daily fluctuation of therapeutic effect agreed with a peak-valley PK profile during a 4-week CDDP regimen, but stabilized after 8-week treatment., Objectives: This article aims to explore the underlying mechanism for the time-dependent drug efficacy of the up-down fluctuation or stabilization in clinic trials., Methods: A rat model of myocardial ischemia was established via isoproterenol induction. Metabolomics was employed to analyze the energy-related substances both in circulatory system and myocardium in the myocardial ischemia model., Results: CDDP treatment ameliorated myocardial ischemia, reversed the reprogramming of the metabolism induced by ISO and normalized the level of most myocardial substrates and the genes/enzymes associated with those metabolic changes. After 1- or 2-week treatment, CDDP regulated plasma and myocardial metabolome in an analogous, time-dependent way, and modulated metabolic patterns of ischemic rats that perfectly matched with the fluctuated or stabilized effects observed in clinical trials with 4 or 8-week treatment, respectively., Conclusion: Metabolic modulation by CDDP contributes to the fluctuated or stabilized therapeutic outcome, and is a potential therapeutic approach for myocardial ischemia diseases.

Anti-ischemic activity of fabomotizole hydrochloride was studied on the model of subendocardial ischemia in rats with endothelial dysfunction. Endothelial dysfunction was modeled by intragastric administration of methionine (3 g/kg, once a day for 7 days). Acute subendocardial ischemia was induced in narcotized rats by intraperitoneal injection of isoproterenol (20 μg/kg/min over 5 min). Fabomotizole hydrochloride (intraperitoneally, 15 mg/kg) significantly reduced isoproterenol-induced ST segment depression in animals with endothelial dysfunction and with intact vasculature.

Purpose of Review: Numerous chemotherapeutic agents have been associated with the development of ischemia and arterial thrombosis. As newer therapies have been developed to treat cancer, some of these chemotherapy drugs have been implicated in the development of vascular disease. In this review, we will summarize the most common chemotherapeutic drug classes that may play a role in the development of ischemic heart disease., Recent Findings: Angiogenesis inhibitors, alkylating agents, antimetabolites, antimicrotubules, and proteasome inhibitors have a number of cardiovascular toxicities. The possible mechanisms of action of these drugs leading to ischemic complications are varied but include endothelial dysfunction, platelet aggregation, reduced levels of nitrous oxide (NO), and elevated levels of reactive oxygen species (ROS), and vasospasm. While some drugs act through multiple pathways that result in the development of ischemic heart disease, others such as the antimetabolites and antimicrotubules appear to primarily cause vasospasm. Furthermore, while aromatase inhibitors increase the risk of heart disease in comparison to tamoxifen in large studies, this finding likely occurs because of a protective role of tamoxifen on cardiovascular risk factors rather than a direct effect of aromatase inhibitors. Angiogenesis inhibitors, alkylating agents, antimetabolites, antimicrotubules, and proteasome inhibitors can lead to ischemic complications in patients with cancer. Many of these drugs have proven to be effective in improving cancer prognosis, but their possible cardiovascular effects have to be carefully monitored and treated. Treatment of ischemic complications in the setting of cancer therapy should focus on the optimal medical management of known cardiovascular risk factors and follow an evidence-based approach.

Background: In patients undergoing regadenoson SPECT myocardial perfusion imaging (MPI), it is unknown how soon and at which dose intravenous aminophylline can be administered to reverse regadenoson-related adverse effects without blunting stress-induced myocardial ischemia., Methods and Results: We analyzed the pooled database of the ASSUAGE and ASSUAGE-CKD trials (n = 548). These were double-blinded, placebo-controlled, randomized clinical trials in which 75 mg of aminophylline or placebo was administered intravenously 90 seconds following 99m Tc-tetrofosmin injection. There were no statistically significant differences in summed difference score (SDS) burden (P = .87) and in the rates of myocardial ischemia (SDS ≥ 2) (P = .93) between the aminophylline (n = 274) and placebo (n = 274) groups. There was no interaction between aminophylline use and SDS as a determinant of the composite endpoint of cardiac death or MI (P = .32) or the composite endpoint of cardiac death, MI, or coronary revascularization (P = .92)., Conclusion: In patients undergoing regadenoson-stress SPECT-MPI, the intravenous administration of 75 mg of aminophylline as early as 90 seconds after radioisotope injection does not seem to attenuate the burden of myocardial ischemia.

Background: It has been suggested that ergoline dopamine agonists can cause ischemic complications. The effect of dopamine agonists in general on the prevalence of ischemic events in patients with Parkinson's disease (PD) has not been studied., Objective: Our aim was to investigate the association between the use of dopamine agonists and hospitalization due to ischemic events in patients with PD., Methods: We performed a nested case-control study using the PHARMO Institute for Drug Outcome Research database. All patients issued at least one prescription for levodopa after the age of 55 years between 1994 and 2006 were initially identified. Cases were patients who were hospitalized for the first time after November 1997 for an ischemic event and were matched to as many as four controls. Exposure to dopamine agonists during the year preceding the index date was identified., Results: The study population consisted of 542 cases and 2,155 controls. The mean effect of dopamine agonist use 1 year prior to the index date on ischemic events requiring hospitalization is shown with 95% probability in the 0.95-1.49 range. Stratified results according to the type of dopamine agonist showed no risk differences between ergoline and nonergoline agonists., Conclusions: This study does not support an association between dopamine agonist use and an increased risk of ischemic events requiring hospitalization.

Toxicological pharmacological study of the molecular complex of nifedipine and glycyrrhizic acid 1:10 (glycidipine) obtained using mechanochemical technique was carried out. High hypotensive and cardioprotective effects of the agent were demonstrated. Chronic administration (45 days) produced no toxic effects in vital organs and systems of Wistar rats and ISIAH rats.

Background: Lithium toxicity is associated with electrocardiogram (ECG) changes, but changes suggestive of an ST segment elevation myocardial infarction have not been reported., Case Report: A 46-year-old incarcerated man suffering from diabetes, hypertension, and schizoaffective/bipolar disorder was treated with lithium 1,200 mg twice daily. Two days prior to presentation the patient became confused, ataxic, and anorexic in jail. Lithium level was 4.69 mmol/L. He was transferred to the emergency department. On arrival, vital signs were normal. The ECG showed a normal sinus rhythm. ST segments were elevated in the anterior leads with downward concavity. T waves were biphasic. Since these changes suggested cardiac ischemia and the patient was unable to respond to questions about chest pain, cardiac enzymes and an emergent echocardiogram were done. Troponin I was less than 0.1 microg/L. Echocardiogram was normal, without wall motion abnormalities. Treatment was with hemodialysis and whole-bowel irrigation. Postdialysis lithium level was 1.30 mmol/L. Over the next several days, electrocardiogram normalized. His speech gradually became coherent. After a 1-week hospitalization, he returned to jail., Conclusion: Lithium intoxication can cause transient ST segment elevations suggesting an acute myocardial infarction. In the absence of a clear history, echocardiogram and cardiac enzymes can be used to rule out a myocardial infarction.

Introduction: Many countries have specific legislation, such as the Controlled Substances Act (1970) in the United States and the Misuse of Drugs Act (1971) in the United Kingdom to control recreational drugs. There is a growing market and supply of "novel" recreational drugs that are not covered under appropriate legislation, despite having similar chemical structures and/or clinical effects. In addition, these novel drugs are often sold legally on the street or through the Internet, with limited details of the exact contents, making application of the appropriate legislation difficult., Case Report: A male patient with no risk factors for ischemic heart disease, presented to our emergency department with agitation and chest pain characteristic of ischemia following the ingestion of two units of "Head Candy." He improved with oral diazepam over a period of 12 hours and there was no biochemical evidence of myocardial damage. Serum analysis demonstrated the presence of diphenylprolinol (diphenyl-2-pyrrolidinemethanol [D2PM]) and glaucine at concentrations of 0.17 mg/L and 0.10 mg/L, respectively. No other recreational drugs were detected in an extensive toxicological screen of blood and urine samples., Discussion: This is the first reported case of confirmed toxicity associated with recreational use of diphenylprolinol in combination with glaucine. In our view, this case provides further support for the need for a systematic approach to toxicological screening of patients with recreational drug toxicity to identify emerging drugs and provide evidence for legislative authorities to assist in revising the legal status of recreational drugs.

Background: Mustard agents are of the major chemical agents used during Iran-Iraq war. There are no reports concerning long-term cardiac effects. The aim was to assess the scintigraphic pattern of myocardial perfusion in patients intoxicated with blistering gases., Method: We analyzed myocardial perfusion scans of 22 consecutive intoxicated patients (21 male and 1 female, all < 44 years) and compared results with 14 controls. Only those patients and controls were entered whose 10-year risk of coronary artery disease (Framingham criteria) was <5%. Also only those patients were experimented upon that had currently other confirmed complications of intoxication (respiratory, cutaneous and ocular complications). All patients underwent a 1-day stress and rest protocol using (99m)Tc-MIBI. Images were assessed visually and quantitatively using Cedars Sinai program., Results: The prevalence of nonhomogeneity of uptake and left and right ventricular enlargement in both visual and quantitative analyses were higher in the mustard exposed patients than unexposed controls. The prevalence of ischemia was higher in the exposed patients (P < 0.05). Cavity to myocardium ratio, as an established and validated measure of ejection fraction, was also significantly lower in the warfare patients than the controls., Conclusion: In so far it lies in our knowledge, this is the first report concerning the scintigraphic pattern of myocardial perfusion in mustard intoxicated patients. Based on the results, the pattern of myocardial perfusion in these patients is significantly different from normal controls, which could resemble either coronary artery disease or mild cardiomyopathic changes.

In this study, we evaluated the impact of the calcium concentration present in the perfusion medium (1.2-3 mM) on contractile performance, lactate dehydrogenase (LDH) release and secondary free radical production during post-ischaemic reperfusion of isolated rat hearts. The impact of calcium concentration on post-ischaemic free radical release was investigated using the Electron Paramagnetic Resonance (EPR) technique and spin trapping with the lipophilic spin trap alpha-phenyl N-tert-butylnitrone (PBN). The evolution of left ventricular end diastolic pressure (LVEDP) in both groups followed the same pattern, but we observed that ischaemic and post-ischaemic contracture was more severe in the group of hearts perfused with 3 mM of calcium as compared with those perfused with 1.2 mM of calcium. A large release of alkyl/alkoxyl species occurred in all hearts from the onset of reperfusion and remained at a high level during the 30 min of reperfusion with no return to basal values. The kinetics and intensity of these releases were the same in both groups. In conclusion, in a range of extracellular calcium levels (1.2-3 mM), the release of alkyl/alkoxyls radicals does not seem to be calcium-dependent. Due to the protective actions of PBN itself, the results of simultaneous investigations of the effects of radical scavengers on isolated heart function may be limited. However, since many pharmacological properties (antioxidant, cellular protector, NO precursor ...) are attributed to PBN, studies investigating oxidative stress with such a multi-faceted tool make interpretation difficult.

Blocking either the Na(+) channel or the Na(+)/H(+) exchanger (NHE) has been shown to reduce Na(+) and Ca(2+) overload during myocardial ischemia and reperfusion, respectively, and to improve post-ischemic contractile recovery. The effect of combined blockade of both Na(+) influx routes on ionic homeostasis is unknown and was tested in this study. [Na(+)](i), pH(i) and energy-related phosphates were measured using simultaneous (23)Na- and (31)P-NMR spectroscopy in isolated rat hearts. Eniporide (3 muM) and/or lidocaine (200 muM) were administered during 5 min prior to 40 min of global ischemia and 40 min of drug free reperfusion to block the NHE and the Na(+) channel, respectively. Lidocaine reduced the rise in [Na(+)](i) during the first 10 min of ischemia, followed by a rise with a rate similar to the one found in untreated hearts. Eniporide reduced the ischemic Na(+) influx during the entire ischemic period. Administration of both drugs resulted in a summation of the effects found in the lidocaine and eniporide groups. Contractile recovery and infarct size were significantly improved in hearts treated with both drugs, although not significantly different from hearts treated with either one of them.

Although the causal relationship between insulin resistance (IR) and hypertension is not fully resolved, the importance of IR in cardiovascular dysfunction is recognized. As IR may follow excess sucrose or fructose diet, the aim of this study was to test whether dietary starch substitution with sucrose results in myocardial dysfunction in energy substrate utilization and contractility during normoxic and post-ischemic conditions. Forty-eight male Wistar rats were randomly allocated to three diets, differing only in their starch to sucrose (S) ratio (13, 2 and 0 for the Low S, Middle S and High S groups, respectively), for 3 weeks. Developed pressure and rate x pressure product (RPP) were determined in Langendorff mode-perfused hearts. After 30 min stabilization, hearts were subjected to 25 min of total normothermic global ischemia, followed by 45-min reperfusion. Oxygen consumption, beta-oxidation rate (using 1-13C hexanoate and Isotopic Ratio Mass Spectrometry of CO2 produced in the coronary effluent) and flux of non-oxidative glycolysis were also evaluated. Although fasting plasma glucose levels were not affected by increased dietary sucrose, high sucrose intake resulted in increased plasma insulin levels, without significant rise in plasma triglyceride and free fatty acid concentrations. Sucrose-rich diet reduced pre-ischemic baseline measures of heart rate, RPP and non-oxidative glycolysis. During reperfusion, post-ischemic recovery of RPP was impaired in the Middle S and High S groups, as compared to Low S, mainly due to delayed recovery of developed pressure, which by 45 min of reperfusion eventually resumed levels matching Low S. At the start of reperfusion, delayed post-ischemic recovery of contractile function was accompanied by: (i) reduced lactate production; (ii) decreased lactate to pyruvate ratio; (iii) increased beta-oxidation; and (iv) depressed metabolic efficiency. In conclusion, sucrose rich-diet increased plasma insulin levels, in intact rat, and increased cardiac beta-oxidation and coronary flow-rate, but reduced glycolytic flux and contractility during normoxic baseline function of isolated perfused hearts. Sucrose rich-diet impaired early post-ischemic recovery of isolated heart cardiac mechanical function and further augmented cardiac beta-oxidation but reduced glycolytic and lactate flux.

Background: Technetium-99m glucarate is a myocardial infarct-avid imaging agent. Recent conflicting and inconclusive reports have suggested that the agent may be taken up by ischemic but viable myocardium. The purposes of this study were (1) to determine conclusively whether there is Tc-99m glucarate uptake in ischemic viable myocardium and (2) to investigate the potential mechanisms for such uptake by studying components of ischemia, namely, low flow, hypoxia, and aglycemia., Methods and Results: Rat hearts were isolated and perfused in a modified Langendorff preparation with a crytalloid perfusate. Tc-99m glucarate was studied in control (n = 6), low-flow (n = 5), hypoxic (n = 5), and aglycemic (n = 5) conditions. The experimental protocol consisted of 20-minute baseline (12 mL/min flow) and 20-minute treatment (low flow at 1 mL/min, hypoxia, or aglycemia), followed by tracer uptake (20 minute) and washout (20 minutes). Activity was monitored with a sodium iodide detector. The tracer was delivered continuously over a 20-minute uptake period. The injected dose was 150 micro Ci (5.6 MBq). Hemodynamics were monitored throughout. Triphenyltetrazolium chloride staining was used to assess myocardial viability. There was no evidence of myocardial necrosis. Low flow tended to delay tracer uptake compared with control for the first 10 minutes, but this did not reach statistical significance. Low flow increased end fractional retention significantly compared with control (mean +/- SEM, 59.0% +/- 0.9% peak vs 41.2% +/- 1.4%, respectively; P <.05). Hypoxia resulted in a trend toward increased uptake; however, this was significant only at one early time point during the uptake phase. Retention in the hypoxia group was similar to control. Tc-99m glucarate uptake was significantly increased in aglycemia from 16 minutes to peak compared with control (1.36% +/- 0.71% injected dose per gram vs 0.91% +/- 0.37% injected dose per gram, respectively; P <.05). Aglycemia produced significantly higher end fractional retention compared with control (51.6% +/- 1.8% peak vs 41.2% +/- 1.4%, respectively; P <.05)., Conclusions: Tc-99m glucarate myocardial retention is increased in the setting of ischemia, even in the absence of necrosis. This increased retention is not due to hypoxia. Furthermore, the retention is only partially explained by tissue hypoglycemia. Thus low flow per se appears to have a role in this increased retention, probably as a result of delayed flow-dependent washout.

It has been recently shown that long-term thyroxine administration increases the tolerance of the heart to ischaemia. The present study investigated whether thyroxine induced cardioprotection involves alterations in the pattern of p38 mitogen activated protein kinase (p38MAPK) and c-Jun NH2-terminal kinases (JNKs) activation during ischaemia-reperfusion. L-thyroxine (T4) was administered in Wistar rats (25 microg/100 g/day, subcutaneously) for 2 weeks (THYR), while normal animals served as controls (NORM). NORM and THYR isolated rat hearts were perfused in Langendorff mode and subjected to 10 or 20 min of zero-flow global ischaemia only and also to 20 min of ischaemia followed by 10, 20 or 45 min of reperfusion. Postischaemic recovery of left ventricular developed pressure at 45 min of reperfusion was expressed as % of the initial value. Activation of p38 MAPK and JNKs was assessed at the different times of the experimental setting by standard Western blotting techniques using a dual phospho p38MAPK and phospho JNKs (p46/p54) antibodies. Activation of p38 MAPK was significantly attenuated during ischaemia and reperfusion in thyroxine treated hearts compared to normal hearts. JNKs were found to be activated only during the reperfusion period. The levels of phospho JNKs were found to be lower in thyroxine treated hearts as compared to untreated hearts, though not at a statistically significant level. Postischaemic functional recovery was higher in THYR as compared to NORM, p < 0.05. In summary, in hearts pretreated with thyroxine, p38 MAPK was attenuated during ischaemia and at reperfusion and this was associated with improved postischaemic recovery of function.

Acute experiments on cats showed that intravenous injection of thyrotropin-releasing hormone prevented blood pressure drop and produced a pronounced antiarrhythmic effect.

K(ATP) channels are present in sarcolemmal and mitochondrial membranes. This study tests the hypothesis that opening mitochondrial K(ATP) channels with Diazoxide (DZ) improves tolerance to cardioplegic ischemia during surgery. Twenty-two rabbit hearts were perfused with Krebs-Henseleit buffer (KHB) on a Langendorff apparatus and underwent 50 min of 37 degrees C global ischemia with St Thomas' cardioplegia (STCP). Hearts were divided into three groups. Ten (control) received no pretreatment. Seven (DZ) received 10 min of 30 microM DZ, a selective mitochondrial K(ATP) opener, in KHB before arrest with STCP containing 30 microM DZ. Five (5-HD + DZ) received 10 min of 100 microM sodium 5-hydroxydecanoate (5-HD), a selective mitochondrial K(ATP) channel blocker, followed by 10 min of 30 microM DZ and 100 microM 5-HD in KHB before arrest with STCP + 30 microM DZ + 100 microM 5-HD. LV developed pressure (LVDP), dP/dt and coronary flow (CF) were measured after 60 min of reperfusion. Diazoxide pretreatment significantly improved the recovery of LV function and coronary flow compared to control (LVDP: 49 +/- 5* vs. 31 +/- 4; +dP/dtmax 927 +/- 93 vs. 507 +/- 85 mmHg/sec*; CF 33 +/- 4 vs. 22 +/- 2 ml/min, *p < 0.05). Mitochondria K(ATP) channel blockade with 5-HD prevented DZ's salutary effect on the recovery of LV and vascular function. Diazoxide pretreatment protects the rabbit heart during cardioplegic ischemia by opening mitochondrial K(ATP) channels. Opening mitochondrial K(ATP) channels may be a new strategy for improving myocardial protection during cardiac surgery.

Background: Technetium 99m-HL91 is a new hypoxia imaging agent that demonstrates increased uptake in ischemic, viable myocardium. This study was performed to determine whether HL91 is taken up by nonviable myocardium., Methods: Twenty-three Krebs-Henseleit buffer-perfused, isolated rat hearts were studied. Tc-99m-HL91 300 microCi was infused over 10 minutes, followed by a 60-minute clearance. Myocardial activity was monitored by use of an NaI crystal. Four groups were studied: control (flow = 12 mL/min, n = 7), low flow (flow = 1 mL/min, n = 6), no flow/reflow (60 minutes no flow/60 minutes reflow before Tc-99m-HL91 infusion, flow = 12 mL/min, n = 5), and cyanide-treated (before Tc-99m-HL91 infusion, flow = 12 mL/min, n = 5). Injury was assessed by creatine kinase, transmission electron microscopy, and triphenyltetrazolium chloride., Results: Control (no injury) and cyanide-treated (severe injury) hearts demonstrated low uptake (6.3+/-0.5 mean+/-SEM and 5.7+/-1.2 microCi, respectively) and low 60-minute retention (13.8%+/-2.2% and 13.7%+/-3.9%, respectively). Low-flow hearts (minimal injury) demonstrated markedly increased uptake (43.5+/-2.8 microCi, P < .01) and increased 60-minute retention (33.2%+/-2.9%, P < .01) compared with control. No-flow/reflow hearts (moderate injury) demonstrated intermediate uptake (8.7+/-0.5 microCi, P < .05 to control), although retention was not significantly different (18.9%+/-3.5%, P = ns). Severely and rapidly injured myocardium demonstrated Tc-99m-HL91 peak uptake and retention indistinguishable from normal. Moderately injured myocardium demonstrated uptake intermediate between severely injured and low-flow-induced ischemic, viable myocardium., Conclusion: Thus Tc-99m-HL91 is not taken up or retained in nonviable and irreversibly injured myocardium.

Isoproterenol hydrochloride (ISO), a beta adrenergic agonist, is known to cause ischemic necrosis in rats. Cardiotoxicity of three different doses of ISO were studied using physiological, biochemical and histopathological parameters. The effects of single and double dose of ISO were analysed, which illustrated that single ISO dose was more cardiotoxic than double ISO dose due to ischemic preconditioning. The tetrapeptide derivatives L-lysine-L-arginine-L-aspartic acid-L-serine (tetrapeptide A) and di-tert.butyloxycarbonyl-L-lysine-L-arginine-L-aspartic acid-tert.butyl O-tert.butyl-L-serinate (tetrapeptide B) along with acetylsalicylic acid as positive control were analysed at different time points for their cardioprotective effect. The results demonstrated that optimal protective effects were observed by pretreatment with 5 mg/kg of tetrapeptide B and this was found to be slightly better than that of acetylsalicylic acid. A lesser degree of cardioprotection was noticed when low doses of tetrapeptide B were administered. This study clearly showed that single dose of ISO (50 mg/kg, s.c.) induced myocardial necrosis could be used as a model to assess cardiovascular drugs and in this model, it was demonstrated that the tetrapeptide B could exhibit optimal cardioprotective effect.

An oxidative insult can induce severe damage, as in the phenomenon of myocardial ischemia and reperfusion. However, there are situations in which the damage is not so obvious (e.g., silent ischemia or aging), and the negative effects will be seen only in time. Our aim was to reveal these small changes in the myofilaments by using the nuclear magnetic resonance (NMR) technique. We used Wistar rat hearts in a constant-pressure Langendorff system, perfused with oxygenated Krebs-Henseleit buffer at 37 degrees C. After 15 minutes of stabilization, the hearts were perfused with buffer supplemented with H2O2 at 50, 75, or 100 micromol/L for 15 or 30 minutes. Fifteen-minute and 45-minute perfusion controls and unperfused hearts were also collected. Heart rate (HR) and left ventricular developed pressure (LVDP) were determined with the help of a latex balloon, inserted in the left ventricle and connected with a pressure transducer. Proton transverse relaxation times (T2) were determined at the end of the experiment. T2 values were measured again in the same tissue fragments after they had been glycerinated and incubated in relaxation and rigor media. The functional parameters (HR, LVDP, coronary flow) were not significantly changed in control and 50 micromol/L H2O2 groups but were increased in the 75 micromol/L H2O2 group and significantly decreased in the 100 micromol/L H2O2 group. T2 is significantly decreased in rigor media starting with 50 micromol/L H2O2 administrated for 30 minutes and does not correlate with dose and duration of the oxidative insult. T2 in rigor is shorter than in relaxation media within the groups, and this difference is increased in the treated hearts.