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Background— Nitric oxide synthase-2 (NOS2) is expressed during acute cardiac allograft rejection in association with myocardial inflammation, contractile dysfunction, and death of cardiomyocytes by necrosis and apoptosis. Recently, allosteric inhibitors of NOS2 monomer dimerization that block NOS2 activity have been developed. Methods and Results— To investigate effects of selective NOS2 blockade, 15 mg/kg of BBS-1 or BBS-2 was administered twice daily subcutaneously to rats starting the day of heterotopic heart transplantation. Cardiac allograft survival was increased significantly, from 6.8 days in controls to 13.3 and to 14.2 days in NOS2-inhibited allografts. At day 5 after heart transplantation, synthesis of NOx was reduced by 53%. There were significantly fewer T lymphocytes and macrophages in the inflammatory infiltrate, as well as less edema and cardiomyocyte damage, and the International Society of Heart and Lung Transplantation score fell from 5 to 4 and 3.5. NOS2 and nitrotyrosine immunostaining and the mean numbers of apoptotic cells and of apoptotic cardiomyocytes were significantly diminished in the treated allografts. Conclusions— The data indicate that selective inhibition of NOS2 dimerization prolongs survival and reduces myocardial inflammation and cardiomyocyte damage in acute cardiac allograft rejection.

Background — Patent foramen ovale (PFO) is associated with stroke, but there are no randomized studies to evaluate the efficacy of antithrombotic therapies. Methods and Results — The PFO in Cryptogenic Stroke Study was a 42-center study that evaluated transesophageal echocardiographic findings in patients randomly assigned to warfarin or aspirin in the Warfarin-Aspirin Recurrent Stroke Study. In this study, 630 stroke patients were enrolled, of whom 312 (49.5%) were randomized to warfarin and 318 (50.5%) to aspirin. Of these, 265 patients experienced cryptogenic stroke and 365 experienced known stroke subtypes. End points were recurrent ischemic stroke or death. PFO was present in 203 patients (33.8%). There was no significant difference in the time to primary end points between those with and those without PFO in the overall population ( P =0.84; hazard ratio 0.96; 95% CI 0.62 to 1.48; 2-year event rates 14.8% versus 15.4%) or in the cryptogenic subset ( P =0.65; hazard ratio 1.17; 95% CI 0.60 to 2.37; 2-year event rates 14.3% versus 12.7%). There was no significant difference among those with no, small, or large PFO ( P =0.41 for small PFO and P =0.16 for large PFO; 2-year event rates for no, small, and large PFO, 15.4%, 18.5%, and 9.5%, respectively). There was no significant difference between patients with isolated PFO and those with PFO in association with atrial septal aneurysm ( P =0.84; 2-year event rates 14.5% versus 15.9%). In patients with PFO, there was no significant difference in the time to primary end points between those treated with warfarin and those treated with aspirin ( P =0.49; hazard ratio 1.29; 95% CI 0.63 to 2.64; 2-year event rates 16.5% versus 13.2%). Conclusions — On medical therapy, the presence of PFO in stroke patients did not increase the chance of adverse events regardless of PFO size or the presence of atrial septal aneurysm.

Introduction: Young women are thought to have low cardiovascular disease (CVD) risk; however, mortality due to ischemic heart disease has actually risen among women aged 35-44 years. We hypothesized that young women with increased CVD risk burden are more likely to misperceive body image and less likely to practice healthful behaviors. Methods: To determine CVD risk burden among young women (aged 18-49 years) of a primarily urban population, 569 women visiting outpatient medical clinics were assessed. Anthropometric measures [height, weight, waist, body mass index (BMI)], attitudes towards weight, and lifestyle behavior were determined. Body image self-perception was assessed using validated silhouette scales. Increased CVD risk burden was defined as presence of hypertension, diabetes mellitus, tobacco use, hyperlipidemia, and/or obesity. Results: Participants were Hispanic (62.7%; 357/569); non-Hispanic White (20.7%; 118/569); non-Hispanic Black (8.9%; 51/569) and Asian/other ethnicity (7.5%; 43/569); mean age was 35.9 years ± 8.1 and income $39,828 ± $20,229. BMI categories were: obese (BMI ≥ 30 kg/m 2 , 27.4%; 155/569); overweight (BMI 25.0 - 29.9 kg/m 2 , 29.0%; 164/569); normal (BMI 18.5 - 24.9, 41.2%; 233/569); and underweight (BMI ≤ 18.4; 2.3%; 13/569). Women without CVD risk burden were the reference standard. Nearly half (47.7%; 271/569) had increased CVD risk burden; and 33.5% (190/569) had ≥ 1 CVD risk factor, exclusive of obesity, including hypertension (18.0%), hyperlipidemia (11.5%), current tobacco use (10.2%), and diabetes mellitus (5.8%). Women with increased CVD risk were less likely to correctly identify body size (48.3% vs. 69.4%, p Conclusion: Paradoxically, though aware of their CVD risk factors and with heightened weight concerns, young women with increased CVD risk burden misperceive their body size and lack healthy behavior knowledge. A disconnect exists between this group’s recognition of their underlying risk and ability to modify their lifestyle to decrease CVD risk burden.

Background —Inflammation may be involved in the origin of transplant coronary artery disease. We hypothesized that plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6), markers for systemic inflammation, would correlate with cardiac transplant graft survival. Methods and Results —We studied 99 consecutive cardiac transplant recipients who were referred for routine endomyocardial biopsy and/or surveillance coronary angiography. Plasma levels of CRP and IL-6 were measured by their respective ELISAs. Patients were divided into 2 groups: those who died or required retransplantation and those who survived without the need for retransplantation. During the follow-up period of 5.0±2.7 years (range, 0.2 to 15.1 years) after transplant, 20 patients died and 9 required retransplantation. There was no significant difference in age, race, sex, cause of native myopathy, presence of diabetes, or use of aspirin, statins, or calcium channel blockers between the 2 groups. Although IL-6 did not relate to graft failure, CRP level was predictive of allograft failure ( P =0.003). The risk of allograft failure increased 36% for every 2-fold increase in CRP level. Moreover, CRP levels also correlated significantly with the frequency of grade 3 rejection ( P =0.02). In multivariate analysis, when combined with other significant predictors such as donor age and sex mismatching of the graft, CRP still significantly predicted graft failure ( P =0.025) with a 32% increase in the risk of graft failure for every 2-fold increase in CRP level. Conclusions —These findings suggest that elevated plasma levels of CRP are associated with subsequent allograft failure in cardiac transplant recipients.

Background —The hypothesis that cyclooxygenase-2 (COX-2) is involved in the myocardial inflammatory response during cardiac allograft rejection was investigated using a rat heterotopic abdominal cardiac transplantation model. Methods and Results —COX-2 mRNA and protein in the myocardium of rejecting cardiac allografts were significantly elevated 3 to 5 days after transplantation compared with syngeneic controls (n=3, P l -lysine. At posttransplant day 5, inhibitor administration resulted in a significant reduction of COX-2 mRNA expression (3764±337 versus 5110±141 arbitrary units, n=3, P P P Conclusions —The data indicates that COX-2 expression is enhanced in parallel with iNOS in the myocardium during cardiac allograft rejection.

Background —The de novo occurrence of sustained ventricular tachycardia (VT) after CABG has been described, but the incidence, mortality rate, long-term follow-up, and mechanism are not well defined. Methods and Results —This prospective study enrolled consecutive patients undergoing CABG at a single institution. Patients were followed up for the development of sustained VT, and a detailed analysis of clinical, angiographic, and surgical variables associated with the occurrence of VT was performed. A total of 382 patients participated, and 12 patients (3.1%) experienced ≥1 episode of sustained VT 4.1±4.8 days after CABG. In 11 of 12 patients, no postoperative complication explained the VT; 1 patient had a perioperative myocardial infarction. The in-hospital mortality rate was 25%. Patients with VT were more likely to have prior myocardial infarction (92% versus 50%, P P P P P P Conclusions —The first presentation of sustained monomorphic VT in the recovery period after CABG is uncommon, but the incidence is high in specific clinical subsets. Placement of a bypass graft across a noncollateralized total occlusion in a vessel supplying an infarct zone was strongly and independently associated with the development of VT.

Background Apoptosis is a distinct form of programmed cell death characterized by activation of endonucleases that cleave nuclear DNA, condensation and fragmentation of nuclear chromatin, blebbing of intact membranes, and cell shrinkage and fragmentation. The mechanisms responsible are unclear, but nitric oxide (NO) generated by inducible NO synthase (iNOS) has been demonstrated to induce apoptosis in macrophages in vitro. This study investigated whether apoptosis occurs during cardiac allograft rejection and examined the relationship of apoptosis to iNOS expression. Methods and Results Heterotopic abdominal transplantation from Lewis to Wistar-Furth rats was used as a model of cardiac allograft rejection; Lewis-to-Lewis grafts served as controls. Apoptosis was identified by DNA ladders after electrophoresis on agarose gels and by in situ labeling of DNA fragments; cell types were determined by immunohistochemistry. The number of apoptotic cardiac myocytes increased sharply from day 3 (0.31/mm 2 ventricular tissue) to day 5 (1.27/mm 2 ) after transplantation. At day 5, allografts showed a significant increase ( P Conclusions Apoptosis of myocardial cells occurs during cardiac allograft rejection. Apoptosis during rejection parallels the expression of iNOS, which suggests that apoptosis may be triggered by NO and peroxynitrite.

Background To evaluate factors that explain sex differences affecting mortality after cardiac transplantation, a retrospective analysis of adult patients undergoing orthotopic cardiac transplantation was undertaken at the Columbia-Presbyterian Medical Center. Methods and Results The study population consisted of 379 patients (75 women, 304 men) ≥18 years of age who survived for ≥48 hours after undergoing orthotopic cardiac transplantation between March 1985 and March 1992. The following were analyzed: incidence of death and treated rejection episodes, donor and recipient cytomegalovirus (CMV) matches, use of OKT3 induction therapy, and donor and recipient HLA mismatches. Women 49±12 years old and men 47±12 years old were characterized by differences in race and diagnosis. Women were more likely to be nonwhite ( P P P =.08). Overall actuarial survival was significantly reduced in women after transplantation ( P P P P Conclusions (1) Women are at risk for reduced actuarial survival up to 3 years after cardiac transplantation. (2) Univariate analysis shows that women are selectively at risk for death when receiving hearts from CMV(+) donors and after receiving OKT3 induction therapy. (3) Multivariate analysis reveals that women are at even greater risk for death when receiving hearts from CMV(+) donors in conjunction with OKT3 induction therapy. (4) In the absence of OKT3 use, the greatest risk of death occurs in CMV(−) women transplanted with CMV(+) donor hearts. (5) When female to male survival curves are compared, factors that influenced survival in women did not appear to be problematic in men.

Background— Drugs that selectively block nitric oxide synthase (NOS) 2 enzyme activity by inhibiting dimerization of NOS2 monomers have recently been developed. Methods and Results— To investigate whether selective inhibition of NOS2 is cardioprotective, rats were pretreated for 2 days with BBS2, an inhibitor of NOS2 dimerization, at 15 mg/kg SC. Isolated buffer-perfused hearts from treated (n=9) and control (n=7) hearts were subjected to 20 minutes of ischemia followed by 60 minutes of reperfusion. NOS2 protein was upregulated in all hearts at the end of ischemia and of reperfusion; NOS2 enzyme activity was 60% lower in hearts from the treated animals. In the treated hearts, the increase in end-diastolic pressure was significantly attenuated at the end of ischemia, and the return of developed pressure at reperfusion was greater ( P P =0.02). At the end of ischemia and of reperfusion, myocardial ATP levels were significantly higher in the treated hearts than in controls ( P P Conclusions— Pretreatment with BBS2, a selective inhibitor of NOS2, improves contractile performance, preserves myocardial ATP, and reduces damage and death of cardiac myocytes during ischemia and reperfusion of isolated buffer-perfused rat hearts.

Background —The contribution of nitric oxide synthase (NOS)-2 to myocardial inflammation and cardiomyocyte necrosis and apoptosis during allograft rejection was investigated through heterotopic cardiac transplantation in mice. Methods and Results —In the first experiments, hearts from C3H donor mice were transplanted into NOS-2 −/− and NOS-2 +/+ C57BL/6J.129J recipients. A second series of experiments included NOS-2 −/− donor hearts transplanted into NOS-2 −/− recipients and wild-type NOS-2 +/+ donor hearts transplanted into wild-type NOS-2 +/+ recipients. (All donors were C57BL/6J and recipients were C57BL/6J.129J.) In the first series of experiments, no significant differences were observed in allograft survival, rejection score, total number of apoptotic nuclei (TUNEL), total number of apoptotic cardiomyocytes, or graft NOS-2 mRNA and protein. Positive NOS-2 immunostaining occurred in endothelial cells and cardiomyocytes in the allografts; the inflammatory infiltrate was NOS-2 positive only when recipients were NOS-2 +/+ . In the second series of experiments, cardiac allograft survival was significantly increased in the NOS-2 −/− mice (26±13 versus 17±8 days, P P P −/− allografts transplanted into NOS-2 −/− recipients. Conclusions —The data suggest that NO derived from NOS-2 contributes to the inflammatory response and to cardiomyocyte damage and apoptosis during acute cardiac allograft rejection.

Background The potential antiatherosclerotic actions of NO were investigated in four groups of mice (n=10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplemental l -arginine and group 4 received l -arginine and N ω -nitro- l -arginine (L-NA), an inhibitor of NO synthase (NOS). Methods and Results Animals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving l -arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly ( P l -arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger ( P l -arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues. Conclusions The data indicate that l -arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects of l -arginine by L-NA suggests that the antiatherosclerotic actions of l -arginine are mediated by NOS. The data suggest that l -arginine may be beneficial in familial hypercholesterolemia.

BACKGROUND Atrial fibrillation (AF) is a commonly encountered arrhythmia in clinical practice, and it occurs frequently after cardiac surgery. The P-wave signal-averaged (SA) ECG noninvasively detects atrial conduction delay. Prior studies have described greater P-wave prolongation in patients with a history of AF, but prospective studies have not been performed. METHODS AND RESULTS Consecutive patients undergoing cardiac surgery were enrolled. The P-wave SAECG was recorded before surgery from three orthogonal leads using a sinus P-wave template and a cross-correlation function. The averaged P wave was filtered with a least-squares-fit filter and combined into a vector magnitude, and total P-wave duration was measured. Patients were observed after cardiac surgery for the development of AF. One hundred thirty patients were enrolled, and 33 (25%) developed AF 2.6 +/- 2.0 days after surgery. Patients with AF more often had left ventricular hypertrophy on ECG (P < .05) and had a lower ejection fraction (P < .05). The P-wave duration on the SAECG was significantly longer in the AF patients than in those without AF: 152 +/- 18 versus 139 +/- 17 milliseconds (P < .001). An SAECG P-wave duration > 140 milliseconds predicted AF with sensitivity of 77%, specificity of 55%, positive predictive accuracy of 37%, and negative predictive accuracy of 87%. The likelihood of experiencing AF was increased 3.9-fold if the SAECG P-wave duration was prolonged. P-wave SAECG results were independent of other clinical variables by multivariate analysis. CONCLUSIONS The P-wave duration recorded with the SAECG is a potent, accurate, and independent predictor of AF after cardiac surgery.

The relationship between resting left ventricular (LV) myocardial blood flow (MBF) and hemodynamic determinants of myocardial oxygen consumption was investigated in 15 patients with multivessel coronary artery disease (CAD) and in 10 patients with normal coronary arteriograms. Mean LV MBF per unit mass of tissue was measured with a multicrystal scintillation camera from the regional clearance rates of xenon-133 injected into the left main coronary artery. Peak LV wall stress, mean velocity of circumferential fiber shortening (Vcf), rate of ejection during the first third of systole (1/3 SV), LV ejection fraction (EF), and the ratio of peak LV systolic pressure to LV end-systolic volume were measured by contrast left ventriculography. Mean LV MBF per unit mass was significantly reduced (48 +/- 11 vs 67 +/- 12 ml/100 g.min; p less than 0.01) in patients with multivessel CAD. However, none of the patients with CAD experienced chest pain or had electrocardiographic evidence of myocardial ischemia during the resting MBF measurements. Ejection phase indexes were lower in the patients with CAD: LVEF (56 +/- 10% vs 64 +/- 7%, p less than 0.05); 1/3 SV (35 +/- 3 vs 44 +/- 4%, p less than 0.05); and mean Vcf (1.05 +/- 0.30 vs 1.19 +/- 0.27 circ/sec, NS). LV wall thickness (9.8 +/- 1.9 vs 7.5 +/- 1.4 mm, p less than 0.01) and LV mass index (94 +/- 32 vs 64 +/- 17 g/m2, p less than 0.05) were significantly increased in the patients with CAD, accounting for the reduction in peak LV wall stress (276 +/- 73 vs 373 +/- 91 dyn-cm-2 x 10(-3), p less than 0.05) observed in these patients. Multiple regression analysis indicated that indexes of three of the major determinants of myocardial oxygen consumption explained 65% of the variation in MBF in patients with CAD: peak LV stress, mean Vcf and heart rate. After adjustment for these three indexes, the average LV MBF rates were not significantly different in the two patient groups (54.8 +/- 1.8 vs 57.6 +/- 2.3 ml/100 g.min). In both groups, resting LV MBF/beat correlated most highly with peak LV wall stress (r = 0.79). Thus, the reduction in LV MBF per unit mass observed in patients with multivessel CAD at rest is related to lower levels of hemodynamic variables that determine myocardial oxygen consumption. Peak LV wall stress is the most important hemodynamic variable determining the level of resting MBF in patients with and without CAD.

Regional myocardial perfusion (RMP) was measured with 133xenon and a multiple-crystal scintillation camera at rest and during atrial pacing in 24 patients with normal coronary arteriograms or less than 50% lesions, Group I, and in 24 with significant (greater than 50% lesions) left coronary artery disease (CAD), Group II. Pacing induced increases in the double product (DP) of heart rate and systolic blood pressure, an index of myocardial oxygen consumption, were not different for Groups I and II. In Group I average mean LV perfusion rate was subnormal at rest but rose from 49 to 73 ml/100 g-min during pacing to 150/min without angina. A response index (RI), (deltaMP X 10(3)/deltaDP), averaged 2.93. Twenty patients in Group II developed angina during pacing. The average mean LV perfusion rose less than in Group I, from 48 to 64 ml/100 g-min (P less than 0.05) and the average RI, 1.76, was lower (P less than 0.01). In 19 of these patients, average RMP distal to the major coronary lesion increased from 46 to 58 ml/100 g-min; this increase during pacing was significantly less than in the remainder of the LV of 48 to 66 ml/100 g-min (P less than 0.05). Average regional RIs were 1.39 and 2.18, respectively. In three patients the presence of collaterals termed adequate by radiological criteria was not associated with preferential decreases in the distal regional RI. The data support the hypothesis that in some patients with CAD, angina pectoris results when an obstructive coronary lesion restricts the total or regional myocardial blood flow response to an increased rate of myocardial oxygen consumption.

Thallium-201 myocardial perfusion scintigraphy was performed after exercise, 4 hours after exercise (redistribution) and after a separate rest injection in 87 patients undergoing coronary arteriography. Significant coronary lesions were present in 62 of the patients. Interpretation of the rest and redistribution scintiscans was the same in 69 patients, 45 of whom had coronary artery disease (CAD). In 16 of the 17 patients with CAD and differing interpretations, defects were present on redistribution scintiscans but not on rest scintiscans; 11 of these patients had evidence of prior transmural myocardial infarction and the other five had an occluded coronary artery supplying the region of the defect. Redistribution scintiscans were more sensitive than rest scintiscans for the detection of prior myocardial infarction (93% vs 54%; P less than 0.01). The increased sensitivity was confined to the detection of prior inferior myocardial infarctions. In 36 of 38 patients with persistent perfusion defects on 4-hour redistribution scintiscans, either a prior infarction or an occluded coronary vessel was present. Exercise scintiscans were compared with rest scintiscans or with redistribution scintiscans for the detection of CAD. The sensitivity was not significantly different with either technique (90% and 89%, respectively), but both scintigraphic techniques were more sensitive than exercise electrocardiography (66%, P less than 0.01). These data demonstrate that redistribution thallium-201 scintiscans may be substituted for conventional rest scintiscans, resulting in reduced cost and radiation exposure to the patient.

Myocardial blood flow (MBF) per unit mass was measured in 10 patients (pts) with severe aortic stenosis (AS) and no significant aortic insufficiency, normal ejection fractions, and normal coronary arteriograms, using xenon-133 and a multiple crystal scintillation camera. MBF per unit mass was reduced in AS (53 +/- 13 mg/100g.min) in comparison to a group of seven normal control patients (69 +/- 12 ml/100g.min) (P less than 0.05). When normalized for heart rate. MBF remained depressed in aortic stenosis (0.65 +/- 0.11 ml/100 g.beat). MBF/beat was strongly related to peak left ventricular wall stress in both groups (r = 0.97). Individual values of MBF/beat were normalized for peak stress using an analysis of covarience; the adjusted mean values were 0.62 +/- 0.03 ml/100g.beat for the AS patients and 0.84 +/- 0.03 ml/100 g.beat for the control patients. There was no overlap between groups in adjusted MBF per beat. Values of MBF per beat and peak stress for a group of ten cardiomyopathy patients with depressed contractility were observed to fall close to the regression line for AS patients. The results suggest that variability in resting MBF in these AS patients is due primarily to differences in LV stress and that reduction in MBF per beat in this group may be due to reduced contractility.

Myocardial blood flow/unit mass (MBF) and the determinants of myocardial oxygen consumption were measured in seven control subjects (group I) and 15 patients (pts) with cardiomyopathy (CM), group II (group IIa-congestive CM: 10 pts; group IIb-hypertrophic CM: 5 pts). In group I left ventricular (LV) MBF was 64 +/- 8 (SD) ml/100g-min; it was significantly lower in IIa (45 +/- 15 ml/100g-min, P less than 0.01) and IIb (39 +/- 7 ml/100g-min, P less than 0.01). However, calculated total LV flow (LV mass X MBF) was increased in the two CM groups. In nine CM pts, LV MBF increased in response to atrial pacing from 41 +/- 7 to 63 +/- 13 ml/100g-min. In group IIa, calculated peak wall stress was normal (4.39 +/hortening (MVcf) was significantly reduced (0.53 +/- 0;18 vs 1.26 +/- 0.12 circum/sec, P less than 0.01). In IIb, MVcf was normal but peak stress was significantly reduced (2.80 +/- 0.75 vs 4.51 +/- 1.10 dynes/cm2 X 10(5), P less than 0.05). Multiple regression analysis based on all pts yielded, MBF - 16.9 MVcf + 9.30 Stress + 0.26 Heart Rate - 26.4 (r=0.79). The data indicate that MBF is reduced in CM patients and the regression analysis suggests that MBF in these 22 pts with normal coronary arteriograms was determined largely by heart rate, peak stress, and ventricular performance.

SUMMARY The effect of myocardial hypertrophy resulting from chronic pressure overload upon myocardial blood flow (MBF) and left ventricular (LV) performance was studied in 17 hypertensive patients, nine of whom had left ventricular hypertrophy (LVH), and nine normotensive controls. Mean LV MBF was measured at cardiac catheterization using the regional xenon-133 washout technique. In hypertensive patients with LVH, LV MBF was reduced at rest (35.0 ± 5.4 ml/100 g/min) compared with controls (64.8 ± 7.6 ml/100 g/min, p < 0.01) and hypertensive patients without LVH (62.6 ± 14.5 ml/ 100 g/min, p < 0.01). Coronary vascular resistance was also elevated in the hypertensive patients with LVH (37.6 ± 6.6 dyn * cm−5g−1, p < 0.01). In contrast, ejection fraction, mean velocity of circumferential fiber shortening(MVcf) and end-systolic and end-diastolic volumes were not significantly different among the three groups. Peak systolic stress was significantly lower (p < 0.01) in the hypertensive patients with LVH (225 ± 45 dyn * cm−2 X 10−8) than in the controls (385 ± 114 dyne cm−2 X 10−8) and the hypertensive patients without LVH (395 ± 39 dyn. cm−2 X 10−8). A multivariate regression equation was developed relating MBF to heart rate (HR), MVcf, and peak LV wall stress: MBF = 22.2 MVcf + 10.6 stress + 0.38 HR- 48.2 (r = 0.89, p < 0.01). When MBF was adjusted for differences in stress among patients using the regression equation, there was no significant difference in MBF between hypertensive patients with and without LVH. These results indicate that (1) resting LV myocardial blood flow is normal in hypertensive patients without LVH; (2) resting MBF Is redSuced in controlled hypertensive patients with LVH as a consequence of reduced wall stress; and (3) resting LV performance measured by ejection phase indexes is well preserved in hypertensive patients with and without LVH. These results also provide additional evidence that resting MBF in patients with normal coronary arteriograms is related to hemodynamic indexes of the major determinants of myocardial oxygen consumption.