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Left ventricular (LV) diastolic function is often impaired in coronary artery disease (CAD). To assess whether verapamil could improve LV diastolic properties, 12 patients with CAD undergoing right-and left-sided cardiac catheterization, as well as simultaneous radionuclide angiography, were studied before and during intravenous administration of verapamil (0.1 mg/kg as a bolus followed by 0.007 mg/kg/min). The heart rate was kept constant by atrial pacing in both studies. LV pressure-volume relations were obtained. Verapamil decreased LV systolic pressure (130 [+ or -] 22 to 117 [+ or -] 16 mm Hg, p (Am J Cardiol 1990;66:818-825), Left ventricular (LV) diastolic function refers to the relaxation phase of the heartbeat, specifically when the left atrium contracts and oxygenated blood flows into the relaxed LV chamber. Angina pectoris (chest pain caused by decreased blood flow to the heart) can impair this function by slowing ventricular relaxation and reducing early filling of the LV. This diastolic dysfunction may induce symptoms of congestive heart failure even when ventricular systolic function (the ability to pump oxygenated blood into the systemic circulation) is normal. The authors investigated whether treatment with verapamil, a calcium channel blocker usually used to treat angina, would reverse diastolic dysfunction. Verapamil is known to improve LV relaxation and filling for some conditions, and noninvasive studies had reported similar effects in patients with coronary artery disease (CAD). It was important to determine whether verapamil-related improvements in LV relaxation and filling were the result of improved diastolic function or increased filling pressure. Twelve patients with CAD, who were undergoing diagnostic heart catheterization and angiography (X-ray), were studied before and during intravenous administration of verapamil. When measurements were being taken, the heart rate was kept constant by a cardiac pacemaker. Comparison with a control group was not possible because healthy people could not be subjected to such invasive procedures. The results of the study indicate that administration of verapamil is useful in treating coronary artery disease. Its effects on the myocardium, or heart muscle, improved LV relaxation and, thereby, increased the peak filling rate. Verapamil also led to a higher preload, resulting in enhanced filling, and reduced afterload, resulting in improved relaxation. Therefore, verapamil affects LV function and early filling as a result of both direct action on the heart muscle and changes in load. (Consumer Summary produced by Reliance Medical Information, Inc.)

The obligatory role of endothelium in mediating vasodilator response to numerous humoral agents has been definitely accepted. However, the chemical identity of endothelium-derived relaxing factor(s) (EDRF) and the mechanisms underlying its synthesis and release remain unclear. Much evidence suggests a compartmentalization of ATP into cells, such that ATP derived from glycolysis or from oxidative metabolism is used for different cellular functions. To investigate which energy source (i.e. oxidativevglycolytic metabolism) is preferentially used for the biosynthesis and/or release of EDRF, rings of rabbit thoracic aorta were studied in organ chambers. After preconstriction with PGF2α, inhibition of glycolysis with either iodoacetate (300μM) (n=6) or 2-deoxyglucose (20 mM) (n=6) did not affect concentration–response curve to the endothelium-dependent agent acetylcholine. In contrast, inhibition of oxidative metabolism with either 1 mmamytal or 5μmrotenone markedly impaired relaxation to acetylcholine. In fact, maximal relaxation was 75±5% in control rings (n=6), and 42±7% (P<0.01) in amytal-treated rings (n=6), whereas rotenone converted acetylcholine relaxation into constriction (n=6;P<0.001). The effect of amytal on endothelium-dependent relaxation was reversible, suggesting that endothelial cells were not damaged by the inhibitor. Amytal also markedly reduced endothelium-mediated relaxation to ADP (37±6%;P<0.05;n=5), as well as to the calcium ionophore A23187. Neither mitochondrial inhibitor affected relaxation to nitroglycerin, an endothelium-independent agent. Finally, amytal did not affect relaxation to S-nitrosocysteine (a recently proposed EDRF) (n=5), suggesting that the effects on acetylcholine and ADP responses were not due to non-specific interferences with EDRF once released from endothelial cells. In conclusion, our data demonstrate that the active process of biosynthesis and/or release of EDRF requires energy derived mainly from mitochondrial oxidative metabolism.

Mepindolol is a newly developed β-adrenergic blocking agent reported to counteract the chronotropic effect of catecholamines, with only little effect on contractility. This study was designed to assess whether or not mepindolol is effective in reducing infarct size. Accordingly, 16 rats, serving as controls, underwent coronary artery occlusion and did not receive any treatment; an additional 19 were treated with mepindolol (1 mg/kg s.c. t.i.d.) for 48 h. Finally, a third group (n 18) underwent sham operation. Forty-eight hours later, infarct size was calculated from left ventricular creatine phosphokinase activity and found to average 52.4 ± 7.8 (mean ± SEM) of the left ventricle in control rats and 35.6 ± 5.4 in treated rats (p < 0.05). Left ventricular phospholipid content averaged 0.79 ± 0.08 μg P/mg protein in sham-operated rats and 0.61 ± 0.04 μg P/mg protein in control animals. In contrast, in mepindolol-treated rats, phospholipid concentration was 0.70 ± 0.04 μg P/mg protein (p < 0.05), this suggesting a protective effect of the drug on ischemia-induced phospholipid degradation. The long-term effect of mepindolol on left ventricular hydroxyproline concentration was assessed 21 days post–coronary occlusion. Infarct size calculated by this method was 30.2 ± 4.8 of left ventricle in 21 control animals and 18.2 ± 4.2 in 28 treated rats (p < 0.05), indicating that, as for the acute necrosis, the extent of scar development after coronary artery occlusion can be reduced by mepindolol.

Elderly patients (≥60 years) with an atrial septal defect (ASD) are a complex subgroup with several haemodynamic limitations. The aim of this study is to describe the clinical and haemodynamic features of these patients and the effectiveness of percutaneous ASD closure in this setting.

The free radical-dependent cardiac toxicity of adriamycin (ADR) is well known. Recently we observed that ADR is also able to affect vascular function, reducing endothelium-dependent relaxation. Moreover, endotheliumindependent relaxation to nitroglycerin (NTG) was also impaired. Therefore, we wanted to investigate the mechanism through which ADR induces impairment of vascular smooth muscle function. In isolated rings of rabbit thoracic aorta preconstricted with 1μM phenylephrine, maximal relaxation to NTG was decreased after 1h incubation with ADR is a dose-dependent manner. In 6 experiments relaxation to NTG was 103±3% in control rings, and was reduced to 97±5% (p=NS), 85±8 (p=NS) and 77±8% (p&lt;0.05) in presence of 30μM, 90M and 150μM ADR. As a consequence, ED50increased from -7.93±0.11 Log Mol NTG in controls to -7.81±0.11 (p=NS). -7.20±0.15 (p&lt;0.05) and -6.99±0.25 Log Mol NTG (p&lt;0.01) with increasing concentrations of ADR. Similar results were observed with two other endothelium-independent vasodilators, SIN-l (which activates guanylate cyclase) and isoproterenol (which activates adenylate cyclase). However, the inhibitory effect of ADR on NTG relaxation was much less pronounced if endothelium was absent. In fact, in denuded rings control maximal relaxation to NTG was 101±3% and after 150 μM ADR it was 89±4% (n=6; P=NS). with no significant changes in ED50. Furthermore, when nitric oxide synthesis in rings with endothelium was inhibited by 300μM L-NAME, maximal relaxation to NTG was not significantly affected, being 100±42% before and 85±44% after 150μM ADR incubation (n=6; p=NS).