Effects of diltiazem on perioperative ischemia, arrhythmias, and myocardial function in patients undergoing elective coronary bypass grafting

Abstract

A prospective, randomized study was performed on 120 patients undergoing elective coronary bypass grafting to define the effect of the calcium channel blocker diltiazem on perioperative ischemia, arrhythmias, and myocardial function. Patients received a continuous 24-hour perioperative infusion of either diltiazem (0.1 mg/kg per hour, n = 60) or nitroglycerin (1 ltg/kg per minute, n =60). Perioperative monitoring included hemodynamic measurements, three-channel Holter monitoring, repeated assessment of 12-lead electrocardiograms, and analysis of ischemia-specific laboratory parameters (creatine kinase, creatine kinase-MB, and creatine kinase-MB-mass and troponla-T), Global and regional systolic function and diastolic compliance were assessed by means of transesophageal echocardiography. The two groups did not differ with respect to preoperative and operative data. Except for a significant reduction in perioperative heart rate, diltiazem had no influence on hemodynamic parameters. The number (17 ± 9 versus 25 ± 5, P < 0.05) and the duration (69 ± 47 versus 104 ± 87 minutes, p < 0.05) of transient ischemic events were significantly reduced as compared with the nitroglycerin group. In addition, peak values of all assessed laboratory parameters except creatine kinase were significantly lower in the diltiazem group. Patients treated with diltiazem had a lower incidence of perioperative atrial fibrillation (5 % versus 18 %, p < 0.05) and lower numbers of ventricular premature beats per hour (10± 8 versus 19 ± 22, P < 0.05) and ventricular runs per hour (5 ± 17 versus 32 ± 38, p < 0.05). Postoperatively, the percent fractional area of contraction and percent systolic wall thickening of the anterior wall were significantly improved in the diltiazem group but not in the nitroglycerin group. In addition, the postoperative diastolic flow/velocity ratio was significantly lower in the nitroglycerin group than in the diltiazem group (0.949 ± 0.391 versus 1.331 ± 0.475, P < 0.001). It is concluded that perioperative infusion of the calcium antagonist diltiazem has no adverse effect on perioperative hemodynamics and systolic myocardial function and provides potent antiischemic and antiarrhythmic protection in patients undergoing coronary bypass grafting.

Postoperative follow-up of coronary artery bypass patients receiving calcium antagonist diltiazem

“…In order to protect the myocardium from ischemic damage, various protective measures have been introduced during recent years such as systemic and local hypo-thermia, anti-and/or retrograde hypothermic crystalloid or blood cardioplegia, and recently, warm blood cardioplegia [8][9][10][11]. Clinical studies have demonstrated the significant antiischemic and antian'hythmic protection of continuous infusion of calcium antagonist diltiazem for patients undergoing coronary bypass grafting [2][3][4][5]. Perioperative calcium antagonist infusion appears to be remarkably effective in improving myocardial protection during and after coronary bypass surgery [t2,13].…”

“…Nevertheless, increasing numbers of patients with more severe coronary artery disease and impaired left ventricular function demand further improvements in perioperative patient management. In previous clinical studies we could demonstrate the significant antiischemic and antiarrhythmic protection of continuous infusion of calcium antagonist diltiazem in patients undergoing coronary bypass grafting [2][3][4][5]. However, prevention of perioperative ischemic events may predict a lower incidence of myocardial infarction or reappearance of angina during postoperative followup, as has been shown for variant or unstable angina in patients with coronary artery disease [6,7].…”

“…Electrocardiographic (ECG) recordings (12-lead) were performed shortly before surgery and 2, 4, 8, 12, 16, 20, 24, 48, 72, and 96 hours after aortic cross-clamp removal. Continuous 3-channel Holter monitoring was performed postoperatively using Zymed Holter recorders and evaluated by the same investigator, blinded to the patient's group assignment, as previously described [3,5]. Rhythm analysis included the incidence of atrial fibrillation and hem1 block and the incidence of ventricular dysrhythmias per hour, defined as ventricular premature complexes (VPC, two ventricular premature beats) and ventricular runs (VR, three or more ventricular premature complexes in succession at a rate between I00 and 200 cycles/ minute).…”

“…Rhythm analysis included the incidence of atrial fibrillation and hem1 block and the incidence of ventricular dysrhythmias per hour, defined as ventricular premature complexes (VPC, two ventricular premature beats) and ventricular runs (VR, three or more ventricular premature complexes in succession at a rate between I00 and 200 cycles/ minute). Different forms of perioperative myocardial ischemia were defined by the combined analysis of ECGs and Holter recordings, as reported earlier [4,5].…”

Nitric oxide homeostasis as a target for drug additives to cardioplegia

“…A number of studies have reported that administration of diltiazem before or during I/R reduces infarct size and protects against reperfusion injury (Klein et al ., 1984; Seitelberger et al ., 1994; Tadokoro et al ., 1996). The beneficial effects of diltiazem on ischemic myocardium are generally thought to be due to coronary artery vasodilatation and a decrease of heart rate as well as cardiac contractility (Ferrari and Visioli, 1991).…”