Failure of adjuvant heparin to reduce myocardial ischemia in the early treatment of patients with unstable angina.

Although the efficacy of long-term administration of antithrombotic agents in unstable angina has been established, short-term effects on myocardial ischemia are unknown. A retrospective analysis was performed in 47 patients undergoing three-channel continuous ST segment monitoring as part of a multicenter trial using esmolol in unstable angina, in which 20 patients received a continuous heparin infusion during the initial assessment of chest pain. Concomitant medications included calcium channel blockers, beta-adrenergic blockers, nitrates, and aspirin in the majority of patients. Clinical variables between the heparin and no heparin groups were similar, except for fewer males and fewer total artery occlusions in the heparin group. No significant differences in the incidence or duration of ischemia were found in a 36 +/- 16 hour monitoring period. Forty percent of the heparin group had 35 episodes of ischemia with a mean of 11 +/- 10 minutes per episode and a total ischemic time of 48 +/- 39 minutes per patient with ischemia. Forty-four percent of the no heparin group had 47 episodes of ischemia with a mean of 13 +/- 13 minutes per episode and a total ischemic time of 58 +/- 47 minutes per patient with ischemia. Multiple linear regression analysis to adjust for intergroup differences did not alter the results. Eighty-five percent of all episodes were asymptomatic. Clinical events, such as episodes of chest pain, emergency coronary arteriography, or coronary revascularization, were also similar between groups. Thus the short-term administration of heparin did not alter the incidence or duration of ischemia in patients with unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained postischemic cardiodepression following magnesium-diltiazem cardioplegia.

Magnesium-diltiazem cardioplegia was evaluated in the intact, perfused rat heart to determine whether the joint administration of these agents would adversely affect myocardial contractile and high-energy phosphate recovery following intermittent, normothermic global ischemic arrest. Sequential metabolic and functional analyses were performed on isolated perfused rat hearts during each phase of the experimental protocol: control (10 min), normoxic cardioplegia (10 min), intermittent global ischemic arrest (two 15-min periods separated by 2 min infusion of the normoxic cardioplegic perfusate), and normoxic postischemic control reperfusion (60 min). Four different cardioplegic solutions were evaluated: 30 mM KCl, 30 mM KCl with 2 mg diltiazem/liter, 20 mM MgCl2, and 20 mM MgCl2 with 2 mg diltiazem/liter. Myocardial phosphatic metabolite levels and intracellular pH were analyzed nondestructively in the intact hearts by phosphorus-31 NMR spectroscopy. Corresponding measurements of peak left intraventricular pressure, rate of peak pressure development (dP/dt), and contraction frequency were performed at the midpoint during each 5-min interval of 31P NMR signal averaging. Magnesium plus diltiazem-treated hearts were distinguished from all other groups by a marked delay in postischemic functional recovery consisting of a prolonged depression in contractility (34% of control, P less than 0.01) that persisted throughout the first 50 min of postischemic reperfusion. Diltiazem in combination with magnesium cardioplegia was detrimental to postischemic functional recovery, despite a rapid restoration of high-energy phosphate stores. The apparent adverse interactive effects of excess magnesium and diltiazem suggest that elective ischemic arrest with magnesium cardioplegia in combination with diltiazem may be contraindicated clinically. The mechanistic basis and drug specificity of this response require further clarification. The present findings appear to exclude ATP and PCr production, and structural causes as the basis for the observed aberrant functional recovery from global ischemia of magnesium plus diltiazem-arrested hearts.