Coronary vasodilatory action after a single dose of nicorandil

Coronary hemodynamics and vasodilatory effects on major epicardial arteries were investigated after a single dose of nicorandil in 22 patients undergoing cardiac catheterization for suspected coronary artery disease. Nicorandil, 20 mg, was administered sublingually to 11 consecutive patients and 40 mg to 11 others. Systemic blood pressure decreased significantly without affecting the heart rate. Coronary sinus blood flow did not change significantly. As the mean aortic pressure decreased significantly by 13% after 20 mg and 21% after 40 mg of nicorandil, the calculated coronary vascular resistance decreased but did not reach statistical significance. There was a decrease in myocardial oxygen consumption (-14% and -22%, respectively), and this was consistent with a significant decrease in the calculated pressure-rate product of 19% and 24%, respectively. A total of 103 selected coronary segments, including 17 stenotic segments, were analyzed quantitatively using a computer-assisted coronary angiography analysis system. After 20 or 40 mg of nicorandil, a significant increase of the mean diameter was observed in the proximal (+9% and +7%), midportion (+10% and +11%) and distal (+15% and +13%) parts of the left anterior descending coronary artery. Corresponding values for the proximal (+13% and +10%) and distal (+10% and +15%) segments of the circumflex artery were observed. An increase in the obstruction diameter was also observed in all but 3 of the analyzed stenotic segments. The results demonstrate that nicorandil, in the route and doses used, causes a significant vasodilation in the major epicardial coronary segments, including most stenotic segments, and decreases the myocardial oxygen demand with little effect on the resistance vessels

Coronary angioplasty early after diagnosis of unstable angina

Coronary angioplasty (PTCA) was performed early after diagnosis of unstable angina in 71 patients who responded favorably with initial pharmacologic treatment and who also had persistent exertional angina. The patients selected for PTCA had predominantly single-vessel disease and a normal or slightly abnormal left ventricular function. PTCA was successful in 87% (62/71) of the patients and unsuccessful in 13% (9/71). There were no deaths related to PTCA. The incidence of myocardial infarction during the procedure was 10% (seven of the 71 patients). Urgent bypass surgery was necessary in 11% (eight of 71 patients) of the patients. All patients were followed up for 12 months. There was one late death and one late nonfatal myocardial infarction. During 12 months of follow-up there was recurrence of angina pectoris in 25% of the patients (14/62). The restenosis rate was 25% (13/52) in the patients with an initial successful PTCA who underwent repeat angiography. Improved cardiac functional status after sustained successful PTCA was demonstrated by the normal exercise capacity on bicycle exercise testing and the absence of ischemia on thallium 201 scintigraphy studies in 70% of the patients. At the 1-year follow-up visit after attempted coronary angioplasty in all 71 patients, the total incidence of deaths was 1.5% (one patient), myocardial infarction 11% (eight patients), and the need for revascularization 25% (emergency surgery eight patients, late surgery three patients, and repeat PTCA seven patients); 91% (64 of 70 patients) were symptom free. It is concluded that PTCA in selected patients with unstable angina initially stabilized with medical treatment is an effective treatment with an acceptable complication rate and an excellent 1-year prognosis

Argatroban During Percutaneous Transluminal Coronary Angioplasty: Results of a Dose-Verification Study.

Background. Thrombin is a key enzyme in thrombogenesis. In animals, specific antithrombotic therapy at the time of coronary angioplasty reduced the incidence of subacute occlusion and inhibited the restenosis response. Argatroban is a highly selective synthetic thrombin antagonist that binds in a competitive manner. This is a report of a dose-verification study, assessing the safety and feasibility of intravenous Argatroban administration in patients undergoing percutaneous transluminal coronary angioplasty. Methods. Before angioplasty an intravenous bolus of 30 g/kg argatroban was administered, followed by a continuous infusion of 3.5 g/kg/min for 72 hours. Bolus injection was repeated, and the infusion rate was increased in order to achieve an activated coagulation time (ACT) of over 300 seconds. Following interim analysis, the bolus and initial infusion rate for the subsequent treatment groups was determined. Study endpoints were the occurrence of adverse events, coagulation tests, and qualitative angiogram reading. Patients were monitored by continuous 12-lead electrocardiographic recording over 24 hours, and underwent control angiography 18–24 hours following angioplasty. Results. Four treatment groups, comprised of 2, 8, 9, and 11 patients, respectively, were studied. The first two patients were excluded from analysis, since the initial dose was ineffective to attain an ACT-authorizing coronary angioplasty. The group with the highest dosage received a 250 g/kg intravenous bolus of argatroban, followed by a 4 hour infusion of 15 g/kg/min. At 4 hours the infusion rate was lowered to 3.8 g/kg/min and was continued for 68 hours without adjustment for catheter removal. The adverse event profile included myocardial infarction, aortocoronary bypass graft, bailout procedures, and repeat coronary angioplasty. Thrombin-time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT) were significantly related to argatroban plasma concentration, as demonstrated by regression analyses (R-square 0.64, 0.71, and 0.84, respectively). Prothrombin fragments 1 and 2 and thrombin-antithrombin III complex did not fit into a mathematical model, but showed slightly increased levels after reduction or cessation of the infusion rate. Conclusions. This dose-verification study, including 30 patients at four dose levels, indicated that argatroban infusion in coronary angioplasty patients can be administered safely, and results in an adequate and predictable level of anticoagulation

Coronary vasodilatory action of elgodipine in coronary artery disease

The effects of intravenous elgodipine, a new second-generation dihydropyridine calcium antagonist, on hemodynamics and coronary artery diameter were investigated in 15 patients undergoing cardiac catheterization for suspected coronary artery disease. Despite a significant decrease in systemic blood pressure, elgodipine infused at a rate of 1.5 micrograms/kg/min over a period of 10 minutes did not affect heart rate and left ventricular end-diastolic pressure. The contractile responses during isovolumic contraction showed a slight but significant increase in maximum velocity (56 +/- 10 to 60 +/- 10 seconds-1; p less than 0.005), whereas the time constant of early relaxation was shortened from 49 +/- 11 to 44 +/- 9 ms (p less than 0.05). Coronary sinus and great cardiac vein flow increased significantly by 15 and 26%, respectively. As mean aortic pressure decreased, a significant decrease in coronary sinus (-27%) and great cardiac vein (-28%) resistance was observed, while the calculated myocardial oxygen consumption remained unchanged. In all, 69 coronary segments (including 13 stenotic segments) were analyzed quantitatively using computer-assisted quantitative coronary angiography. A significant increase in mean coronary artery diameter (2.27 +/- 0.53 to 2.48 +/- 0.53 mm; p less than 0.000001), as well as in obstruction diameter, (1.08 +/- 0.29 to 1.36 +/- 0.32 mm; p less than 0.02), was observed. The results demonstrate that elgodipine, in the route and dose described, induces significant vasodilatation of both coronary resistance and epicardial conductance vessels, without adverse effects on heart rate, myocardial oxygen demand and contractile indexes

Acute effects of intravenous nisoldipine on left ventricular function and coronary hemodynamics

The hemodynamic effects of nisoldipine were investigated in 16 patients with suspected coronary artery disease who underwent routine cardiac catheterization. Nisoldipine was given intravenously in a dose of 6 micrograms/kg over 3 minutes and measurements made before and after drug administration during spontaneous and matched atrial paced heart rate. During sinus rhythm, nisoldipine produced a significant increase in heart rate (19%, p less than 10(-5]. Left ventricular systolic pressure decreased 28% (p less than 10(-6) and left ventricular end-diastolic pressure did not change significantly (5%, difference not significant). Coronary sinus and great cardiac vein blood flow increased by 21% (p less than 0.02) and 25% (p less than 0.005), respectively, after nisoldipine administration. Simultaneously, mean aortic pressure decreased 33% (p less than 10(-6]; consequently, the global and regional coronary vascular resistances decreased by 50% (p less than 10(-4]. The decreases in global (-8%) and regional (-4%) myocardial oxygen consumption did not reach statistical significance. A 6% (not significant) increase in end-diastolic volume and an 11% (p less than 0.002) decrease in end-systolic volume resulted in an increase of 21% in stroke volume (p less than 10(-4] with a consistent increase in ejection fraction (+16%, p less than 10(-5]. Total systemic vascular resistance was reduced by 30% (p less than 0.0002). During spontaneous heart rate and matched atrial pacing, the time constant of isovolumic relaxation as assessed by a biexponential model, was significantly shortened.(ABSTRACT TRUNCATED AT 250 WORDS

Acute effects of intravenous nisoldipine on left ventricular function and coronary hemodynamics

The hemodynamic effects of nisoldipine were investigated in 16 patients with suspected coronary artery disease who underwent routine cardiac catheterization. Nisoldipine was given intravenously in a dose of 6 micrograms/kg over 3 minutes and measurements made before and after drug administration during spontaneous and matched atrial paced heart rate. During sinus rhythm, nisoldipine produced a significant increase in heart rate (19%, p less than 10(-5]. Left ventricular systolic pressure decreased 28% (p less than 10(-6) and left ventricular end-diastolic pressure did not change significantly (5%, difference not significant). Coronary sinus and great cardiac vein blood flow increased by 21% (p less than 0.02) and 25% (p less than 0.005), respectively, after nisoldipine administration. Simultaneously, mean aortic pressure decreased 33% (p less than 10(-6]; consequently, the global and regional coronary vascular resistances decreased by 50% (p less than 10(-4]. The decreases in global (-8%) and regional (-4%) myocardial oxygen consumption did not reach statistical significance. A 6% (not significant) increase in end-diastolic volume and an 11% (p less than 0.002) decrease in end-systolic volume resulted in an increase of 21% in stroke volume (p less than 10(-4] with a consistent increase in ejection fraction (+16%, p less than 10(-5]. Total systemic vascular resistance was reduced by 30% (p less than 0.0002). During spontaneous heart rate and matched atrial pacing, the time constant of isovolumic relaxation as assessed by a biexponential model, was significantly shortened.(ABSTRACT TRUNCATED AT 250 WORDS

Recovery of regional myocardial dysfunction after successful coronary angioplasty early after a non-Q wave myocardial infarction

More aggressive therapy has been suggested for patients who have a non-Q wave myocardial infarction (MI) because of the frequency of subsequent unstable angina, recurrent MI, and high mortality rate compared to patients with Q wave MI. The present study was undertaken to investigate the effect of coronary angioplasty on regional myocardial function of the infarct zone in patients with angina early after a non-Q wave MI. The study population consisted of 36 patients undergoing successful coronary angioplasty within 30 days of a non-Q wave MI, in whom sequential left ventricular angiograms of adequate quality were obtained before the initial procedure and at follow-up angiography. The global ejection fraction increased significantly from 60 +/- 9% to 67 +/- 6% (p = 0.0003). This significant increase in the global ejection fraction was primarily due to a significant improvement in the regional myocardial function of the infarct zone. The results of the present study show not only that ischemic attacks early after a non-Q wave MI may lead to prolonged regional myocardial dysfunction but more important that this depressed myocardium has the potential to achieve normal contraction after successful coronary angioplasty

Effects of successful percutaneous transluminal coronary angioplasty on global and regional left ventricular function in unstable angina pectoris

Sixty-eight patients (58 men, 10 women, mean age 56.3 years, range 31 to 72) with unstable angina pectoris, either initially stabilized with or refractory to optimal pharmacologic treatment, were studied to determine whether regional dysfunction due to stunning of the myocardium caused by attacks of chest pain at rest could be improved with percutaneous transluminal coronary angioplasty (PTCA). Patients were included in the study if they had successful 1-vessel PTCA, no angiographic restenosis, no reocclusion or late myocardial infarction and 2 serial left ventriculograms of sufficient quality to allow automated contour analysis before and after PTCA. Global ejection fraction increased significantly (from 56% to 60%, p less than 0.05) only after successful dilatation of a stenosis of the left anterior descending coronary artery. Analysis of regional wall displacement showed significant improvement of regional wall motion in the areas supplied by the dilated vessel of either the left anterior descending, the left circumflex or the right coronary artery. Thus, regional myocardial dysfunction due to stunning of the myocardium in patients with unstable angina improves after successful PTCA

Percutaneous transluminal angioplasty of a totally occluded venous bypass graft: a challenge that should be resisted

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Percutaneous transluminal coronary angioplasty for angina pectoris after a non-Q-wave acute myocardial infarction

Despite initially favorable prognosis in patients with non-Q-wave acute myocardial infarction (AMI), long-term mortality in this subset of patients appears to be similar to or even greater than that in patients with Q-wave AMI. The relatively poor late prognosis is primarily due to a high incidence of unstable angina and recurrent AMI. Between January 1982 and January 1987, 114 patients with suitable coronary narrowing underwent percutaneous transluminal coronary angioplasty (PTCA) for angina pectoris (present either at rest or during mild exertion, and despite optimal pharmacologic therapy), a median of 31 (range 2 to 362) days after a non-Q-wave AMI. Success was achieved in dilating the obstructed artery in 98 patients (113 of the 129 dilated arteries). Emergency bypass surgery was performed in 7 patients. Mean clinical follow-up of 20 (range 3 to 59) months was obtained in all patients and revealed no deaths. Of the 98 patients with successful PTCAs, 6 (6%) developed a nonfatal recurrent AMI and 62 (63%) were asymptomatic. However, recurrent angina affected 31 patients (32%) and was treated by repeat PTCA (n = 18), coronary bypass surgery (n = 5) or pharmacologic therapy (n = 8). At follow-up, 74% of the patients (73 of 98) were asymptomatic after a successful PTCA and, if necessary, a repeat PTCA, without incidence of recurrent AMI, coronary bypass surgery or death. The high initial success rate, low incidence of subsequent death and late recurrent AMI and sustained symptomatic benefit suggest that PTCA is an effective initial treatment strategy in these selected patients