Diltiazem provides anti-ischemic and anti-arrhythmic protection in patients undergoing coronary bypass grafting.

In 91 patients undergoing elective coronary bypass grafting, the anti-ischemic and anti-arrhythmic efficacy of a 24-hour infusion of either the calcium antagonist diltiazem (0.1 mg/kg per h, n = 44) or nitroglycerin (1 micrograms/kg per min, n = 47) were compared. Myocardial ischemia was diagnosed by Holter monitoring and the repeated assessment of 12-lead ECG and serum enzyme levels and defined as a transient ischemic event, transient coronary spasm or myocardial infarction. The two groups did not differ with respect to preoperative and operative data. Postoperatively, the average heart rate and pulse pressure rate were significantly lower in the diltiazem group. The incidence of postoperative atrial fibrillation (4.5 vs 19.1%, P < 0.01), transient coronary spasm (2.3 vs 11.4%, P < 0.05) and myocardial infarction (4.5 vs 8.5%, not significant) and the frequency of ventricular premature couplets/h (12.1 +/- 4.5 vs 18.1 +/- 5.1, P < 0.05) and ventricular runs/h (2.5 +/- 0.8 vs 6.5 +/- 2.8, P < 0.05) were lower in the diltiazem as compared to the nitroglycerin group. In addition, diltiazem-treated patients had significantly lower postoperative peak values of creatine kinase-MB (19.3 +/- 11.6 vs 29.3 +/- 20.6, P < 0.05). In conclusion, perioperative infusion of diltiazem is effective in reducing the incidence and extent of arrhythmias and myocardial ischemia in patients undergoing elective coronary bypass grafting as compared to patients receiving nitroglycerin.

Myocardial energetics in dilated cardiomyopathy.

To assess hemodynamic and energetic effects of different drug interventions on idiopathic dilated cardiomyopathy (IDCM), we determined hemodynamic variables of myocardial oxygen consumption (MVO2) in 37 patients with IDCM. Hemodynamics were measured during routine left and right heart catheterization. MVO2 was analyzed from myocardial blood flow (measured by the argon method) and aortocoronary sinus blood oxygen difference. The hemodynamic variable which correlated best with MVO2 was shown to be the systolic stress time integral (STI). Four different representative compounds were tested with respect to their acute effects on myocardial energetics (MVO2/STI) in patients with IDCM who were in compensated heart failure (NYHA class II-III). The drug interventions were performed at rest. Intravenous injection of the vasodilator nitroprusside yielded a 35% reduction in STI and a 30% reduction in MVO2; in other words, the ratio MVO2/STI was not altered. Injection of the calcium sensitizer and phosphodiesterase inhibitor pimobendan also did not alter this ratio, as both STI (36%) and MVO2 (33%) were lowered. The profound reduction in STI (60%) seen with the phosphodiesterase inhibitor enoximone was accompanied by a much smaller decrease in MVO2 (19%); therefore, the ratio of MVO2/STI increased significantly. An increase of this ratio was also seen with the partial beta-1 receptor agonist xamoterol. However, in this case STI did not change, whereas MVO2 increased by 26%. In summary, vasodilation has energy-saving effects, whereas positive inotropism is an energy-consuming process. We conclude that the overall effect on myocardial energetics of a drug which possesses both positive inotropic and vasodilating properties depends on the balance of the two properties.

Modulation of myothermal economy of isometric force generation by positive inotropic interventions in the guinea pig myocardium.

Isometric force development has been measured simultaneously with liberated heat in papillary muscles from the right ventricle of the guinea pig, using rapid antimony-bismuth thermopiles. The following components of the contractile cycle and their relation to energy consumption were evaluated: (1) basal metabolism; (2) crossbridge cycling; (3) calcium cycling; and (4) recovery processes. The influences of isoproterenol, high calcium and UDCG-115, a calcium-sensitizing substance, on these four energy compartments of the muscle were studied relative to their positive inotropic effects. Isoproterenol increased initial heat per peak developed tension or per tension-time integral from 7.4 +/- 1.55 to 11.65 +/- 1.15 mucal/g cm (p less than 0.02) or from 4.52 +/- 0.79 to 8.14 +/- 0.77 mucal/g cm sec (p less than 0.01), respectively. In contrast, these ratios were unchanged from control values by positive inotropic interventions with 11 mM calcium or UDCG-115. The increase of initial heat for a unit of mechanical activity due to isoproterenol is attributable to activation and contractile protein processes, i.e. the activation heat increased from 0.24 +/- 0.05 to 0.68 +/- 0.13 mcal/g (p less than 0.01) and tension-dependent heat per tension-time integral increased from 2.24 +/- 0.60 to 5.18 +/- 0.89 mucal/g cm sec (p less than 0.01). We conclude that isoproterenol increases the number of calcium ions released into the sarcoplasm during each activation cycle. It also alters the rate of crossbridge cycling associated with a decreased economy of force generation.(ABSTRACT TRUNCATED AT 250 WORDS)