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Background: Spinal cord stimulation (SCS) is effective in the treatment of severe coronary artery disease (CAD) unresponsive to anti-anginal medication or revascularization procedures. However, there is still concern about its safety., Objective: To investigate the reliability, morbidity, and mortality aspects of SCS in patients with refractory angina pectoris by studying the predictors of outcome, defined by efficacy, adverse events and mortality, in patients with CAD and SCS., Methods: Fifty-seven patients (18 women) treated with SCS, aged 59.8 +/- 7.6 years (mean +/- SD) were studied retrospectively. They had suffered from manifest CAD for 9.4 +/- 4.9 years; 46 of them had experienced a myocardial infarction prior to the implantation; 28 had had a previous percutaneous transluminal coronary angioplasty; and 52 had undergone coronary artery bypass surgery. The mean left ventricular ejection fraction was 51.8 +/- 13.8%. All of the patients were being treated with two or three anti-anginal drugs., Results: During 2042 patient-months follow-up, nine of the 57 patients died (annual mortality rate 6.5%). The percentage of adverse events requiring reprogramming or surgical reintervention was reduced from 83% for 18 patients with the Medtronic ITREL lead to 33% for 39 patients with the ITREL II system. The clinical outcome was correlated positively with a left ventricular ejection fraction > 40% (P = 0.0005), and negatively with a high cholesterol level (P = 0.0042), more prior revascularizations (P = 0.028), and a higher New York Heart Association classification (P = 0.04)., Conclusions: Improvement of the SCS system reduced the equipment-related complication rate. The predictors of outcome are related to the traditional risk factors for CAD. The mortality rate of patients with refractory angina treated with SCS is similar to that of patients with CAD and stable angina pectoris.

Basophilic or mucoid degeneration of the intima in the coronary arteries is an extremely rare cause of premature atherosclerosis. An unusual case of fatal basophilic degeneration of the coronary arteries 142 days after delivery is reported.

The delivery of new Palmaz-Schatz stents in native coronary arteries can be facilitated by using the technique of deep seating of a 6 French guiding catheter. Two patient histories are described to illustrate this new technique.

Background: Treatment of patients with acute myocardial infarction should aim to restore blood flow in the infarct-related artery as soon as possible. Thrombolytic therapy has recently been compared with direct angioplasty; however, these interventions may not be sufficient, and coronary artery bypass grafting (CABG) may be necessary., Methods: In a series of 301 patients with acute myocardial infarction, randomly assigned either to receive intravenous streptokinase (n = 149) or to undergo percutaneous transluminal coronary angioplasty (PTCA; n = 152), 31 patients (aged 61 +/- 10 years; 27 men, four women) underwent CABG within 6 weeks of acute myocardial infarction., Results: Twelve patients (nine in the PTCA group and three in the streptokinase group) underwent surgery within 48 h of the onset of symptoms. Bypass surgery was performed in the streptokinase group on failure of thrombolytic therapy (n = 2), recurrent ischemia (n = 4), or postinfarct angina (n = 9). In the PTCA group, CABG was performed for left main stenosis (n = 6), failed PTCA (n = 3), recurrent ischemia (n = 2), or postinfarct angina (n = 5). An intra-aortic balloon pump (IABP) was required in 15 patients (five streptokinase and 10 PTCA). Major complications after CABG were more common among patients who underwent surgery within 48 h than those after 48 h (eight in 12 patients versus four in 19, respectively). After 17.0 +/- 8.6 months (range 3-33 months), two patients had died; one of end-stage heart failure after 3 months, and one of a stroke after 16 months (both were in the PTCA group and one had undergone surgery within 48 h). One patient suffered a reinfarction after 11 months and one a non-fatal stroke after 1 month (both underwent CABG within 48 h). The left ventricular ejection fraction did not differ between the groups (43 +/- 15% for the 'early' group and 42 +/- 11% for the 'late' group)., Conclusion: CABG can be performed safely and effectively after initial treatment with direct angioplasty or thrombolytic therapy after acute myocardial infarction. If it is performed within 48 h of onset of symptoms, (in-hospital) morbidity is higher, without affecting mortality or left ventricular function.

In this study, normal values for signal averaged electrocardiographic parameters were assessed in healthy pigs (n = 100) and the development of late potentials after myocardial infarction (n = 41) in relation to inducible ventricular tachycardia was investigated. Normal values are: filtered QRS duration (QRS) < or = 78 msec; root mean square voltage of the averaged QRS complex (V(tot)) > or = 51 microV, and duration of terminal activity below 30 microV (D30) < or = 37 msec. The distribution of the root mean square voltage in the last 30 msec (V30) was biphasic. Two weeks after myocardial infarction, QRS was prolonged from 55 +/- 10 to 66 +/- 19 msec (P < 0.002). D30 was prolonged from 19 +/- 6 msec to 28 +/- 13 (P < 0.002). V30 was decreased from 107 +/- 135 microV to 45 +/- 77 (P < 0.02). The total voltage (V(tot)) was decreased from 195 +/- 78 to 123 +/- 61 microV (P < 0.002). In four pigs (19%) late potentials developed. Sustained ventricular tachycardia was inducible in 11 pigs (52%), ventricular fibrillation in two pigs (10%) and eight pigs (38%) were noninducible. Three of 11 inducible pigs and one of the noninducible pigs had a late potential. The incidence of late potentials and their relation to inducible sustained ventricular tachycardia is comparable to the situation in man. Therefore, this pig model is an attractive alternative to the commonly used dog models.

The effects of early reperfusion were studied in closed-chest pigs subjected to either 45 min or 3 hr of regional ischemia. Myocardial enzyme release during early reperfusion and electrophysiological stability after two weeks were assessed. Coronary artery occlusion durations of 3 hr and early reperfusion after 45 min were compared. The creatine phosphokinase levels in the coronary effluent were lower after early reperfusion (p less than 0.001). Moreover, in the early reperfusion group, the coronary sinus catecholamine and purine levels rose to higher values than in the 3 hr group. The plasma levels of catecholamines and the plasma renin activity increased rapidly but transiently at reperfusion in the 45 min group. Both the rate-pressure product and the heart rate were elevated at the end of the reperfusion period (p less than 0.001) in the 45 min group. Survival for two weeks was 3 out of 6 animals in the 3 hr group and 5 out of 8 in the 45 min group. In all but one surviving animal, sustained ventricular tachycardias were inducible by programmed stimulation. Abnormally low QRS amplitudes and delayed potentials were found in the signal-averaged electrocardiogram in the early reperfusion group only. In conclusion, early reperfusion causes a reduction of myocardial tissue damage, but simultaneously, neurohumoral parameters showed a greater activation of the sympathetic nervous system and the renin-angiotensin system apparently causing a deleterious increase in oxygen consumption. Therefore, this injurious component of early reperfusion might prevent the potentially beneficial effects of a reduced tissue damage on survival or late arrhythmias.

The regulation of coronary hemodynamics is a complex process. One important factor that interferes with the regulation of coronary tone is the pathophysiological state of the vessels: stimuli that in normal vessels provoke no or only a slight vasoconstriction may cause a severe vasoconstriction in diseased vessels. This effect is related to the function of the endothelium and its ability to produce nitric oxide and prostaglandins. The presence of a local renin-angiotensin system implies the possibility of influencing the coronary flow via interference with this local system. Therefore, it is interesting to determine the effects of converting enzyme inhibitors on coronary flow. In animal experiments, a bradykinin-dependent coronary vasodilation by angiotensin-converting enzyme (ACE) inhibitors is suggested. However, reports on the effect of converting enzyme inhibitors in patients with angina pectoris are not consistent. Some authors found an increase in coronary flow and others found no change or a decrease. The importance of the activation of the renin-angiotensin system is discussed. Moreover, it is shown that captopril reduces sympathetic-mediated coronary vasoconstriction during the cold pressor test and that captopril enhances the parasympathetic-mediated bradycardia during the diving response. In conclusion, the effects of converting enzyme inhibitors on coronary flow is an interesting but not fully understood topic. Therefore, the multifactorial mechanism of action of converting enzyme inhibitors deserves further investigation. There are probably subgroups of anginal patients who may benefit from converting enzyme inhibitor therapy. These subgroups have to be defined. Especially, the finding that a converting enzyme inhibitor reduces sympathetically induced coronary vasoconstriction seems promising.

In this study, the vasodilating properties of captopril and zofenoprilat, two angiotensin-converting enzyme (ACE) inhibitors containing the sulfhydryl group, are investigated in the isolated rat heart. It is demonstrated that both compounds increase coronary flow in a dose-dependent manner. However, the mean pD2 of zofenoprilat appears to be significantly higher than the mean pD2 of captopril (4.55 +/- 0.06 and 3.35 +/- 0.02 respectively), indicating that zofenoprilat is about ten times more potent in increasing coronary flow than captopril. Possibly this difference in potency between captopril and zofenoprilat can be explained by their physicochemical properties. Since zofenoprilat is more lipophilic than captopril, its concentration in cardiac and vascular tissues at distribution equilibrium is thought to be higher than the tissue concentration of captopril, which may result in a more pronounced vasodilatory action. The precise mechanism of coronary vasodilation induced by ACE inhibitors containing the sulfhydryl group is not yet understood. Several factors have been proposed, such as stimulation of prostacyclin production. However, in this study, concomitant administration of 10(-6) mol/l acetylsalicylic acid shows no antagonism, indicating that under normoxic conditions the vasodilatory effects of captopril and zofenoprilat are independent of the production of vasodilating prostaglandins. Therefore, other factors than stimulation of prostacyclin synthesis seem to be involved, such as prevention of bradykinin breakdown and/or potentiation of endothelium derived relaxing factor (EDRF). Furthermore, despite a marked inhibition of prostacyclin production, 10(-6) mol/l acetylsalicylic acid itself has no effect on coronary flow. These results suggest that prostacyclin does not play an important role in the regulation of coronary flow, at least in the normoxic isolated rat heart.

We studied the in vivo effect of bradykinin infusion on inducible sustained ventricular tachycardia (VT) 2 weeks after myocardial infarction in pigs, based on the assumption that the antiarrhythmic effect of angiotensin-converting enzyme (ACE) inhibitors may, apart from their angiotensin-II lowering effect, also be due to elevation of endogenous bradykinin levels. Of the six pigs with inducible VT in the control state, four were noninducible during subsequent bradykinin infusion (p less than 0.05). The ventricular effective refractory period (VERP) did not change during bradykinin infusion (from 237 +/- 37 to 239 +/- 42 ms), nor did intraventricular conduction change (filtered QRS duration was 45 +/- 17 ms before and 43 +/- 19 ms during infusion). Bradykinin caused both a significant systolic blood pressure (SBP) decrease (from 79 +/- 14 to 49 +/- 4 mm Hg, p less than 0.001) and diastolic BP (DBP) decrease (from 41 +/- 10 to 27 +/- 4 mm Hg, p less than 0.01). In conclusion, exogenous bradykinin reduced the inducibility of sustained VT 2 weeks after myocardial infarction. Because refractory periods or conduction velocity were not affected, the mechanism of action might be associated with the BP decrease, which can decrease wall stress. The previously reported antiarrhythmic effect of ACE inhibitors may be due in part to elevation of endogenous bradykinin levels.

In this study, the effect of bradykinin or saline infusion during ischemia and reperfusion on electrical stability, 2 weeks after myocardial infarction, was assessed. Acute myocardial infarction was induced in 21 pigs by a transluminal occlusion of the left coronary artery with a catheter balloon, inflated for 45 min. Bradykinin was administered by a 30-min infusion that started after 30 min of coronary occlusion and was continued until 15 min after reperfusion. Although creatine kinase levels in bradykinin-treated animals were significantly lower (p less than 0.001), 2 week survival was not different between groups. In survivors, the filtered QRS (ventricular deflection) duration (detected using signal-averaged electrocardiography) was significantly prolonged in saline-treated pigs, whereas in bradykinin-treated pigs this prolongation was prevented. The terminal voltage of the QRS complex was significantly lower in saline-treated pigs than in bradykinin-treated pigs. These two parameters signify an improved electrical stability after bradykinin treatment. Refractory periods in saline-treated hearts were longer than in bradykinin-treated hearts (106 +/- 10% vs. 95 +/- 13%, p less than 0.05). Also, current thresholds in the infarct border zones showed a greater variance in saline-treated hearts (p less than 0.001), pointing toward more tissue heterogeneity of the infarct border zone. Programmed electrical stimulation showed a trend toward reduced inducibility of sustained ventricular tachycardia in bradykinin-treated hearts. Therefore, bradykinin improves electrical stability weeks after experimental myocardial infarction.

Exogenous bradykinin was administered to pigs in which an experimental infarction was evoked by ischemia and reperfusion. Ischemia (45 min) was induced in a closed-chest model with a balloon catheter in the left anterior descending artery, reperfusion by deflating and removing the balloon. The pigs were treated with saline (n = 11) or bradykinin (0.1 mg/kg in 30 min) infusion (n = 10) during the last 15 min of the ischemic period and the first 15 min of reperfusion. During ischemia, heart rate increased in the saline group to 120 +/- 9% of the initial value (p less than 0.05) and in the bradykinin group to 155 +/- 13% (p less than 0.05). After reperfusion, the rate-pressure product was increased in both groups. The increase of arterial creatine kinase levels was significantly less in the bradykinin-treated group. However, the catecholamine and purine levels were increased, as was the plasma renin activity when compared with the saline group. Two weeks after the infarction, six pigs had died in each group. In three out of five surviving saline-treated pigs and one out of four surviving bradykinin-treated pigs, a sustained ventricular tachyarrhythmia was inducible after programmed electrical stimulation. In conclusion, although systemically administered bradykinin caused a temporary increase in myocardial ischemia, it did reduce the (enzymatic indices of) infarct size. Therefore, the beneficial effects, previously found for ACE-inhibitors might at least partially be related to the potentiation of endogenous bradykinin.

The effects of oral zofenopril pretreatment were investigated in a chronic closed-chest pig model of ischemia and reperfusion. Pigs (25-35 kg) were pretreated orally with zofenopril (15 mg/day) on the 2 days prior to ischemia, which was evoked by the inflation of a catheter balloon in the left anterior descending coronary artery over 45 minutes. The catheter was then removed and the myocardium was reperfused. After 2 weeks, infarct properties were assessed by signal averaging of the body surface electrocardiogram and the inducibility of malignant ventricular tachyarrhythmias was tested with a programmed electrical stimulation protocol. A significant increase in the pressure-rate product (43 +/- 11%, mean +/- SEM), indicating the oxygen demand of the heart, was prevented by zofenopril (19 +/- 8%, p less than 0.05). Zofenopril reduced the peak efflux of adrenaline (1302 +/- 213 vs. 3201 +/- 760 pg/ml; p less than 0.05), noradrenaline (402 +/- 54 vs. 902 +/- 282 pg/ml; p less than 0.05), and of the adenosine catabolites inosine and hypoxanthine (56 +/- 4 vs. 78 +/- 9, pg/ml; p less than 0.05) in the coronary venous effluent. The efflux of the cytoplasmatic enzyme creatine phosphokinase was not significantly reduced after zofenopril (p = 0.08). No difference in plasma renin levels between the groups were found. After 2 weeks, late potentials were found only in the surviving animals from the untreated group, i.e., the voltage vector magnitude was more reduced, and a prolongation of the QRS duration and of the terminal low-amplitude part of the high-frequency QRS were found.(ABSTRACT TRUNCATED AT 250 WORDS)

The calcium-entry blocker isradipine was tested in a closed-chest pig model for chronic myocardial infarction. Ischemia was evoked in anesthetized pigs (25-35 kg) by inflating a catheter balloon in the left anterior descending coronary artery for at least 45 min. Hemodynamic monitoring and signal averaging of X, Y, and Z electrocardiographic leads were performed (150 beats, filtered at 50 Hz). After reperfusion, all animals developed an accelerated idioventricular rhythm and high creatine kinase (CPK) plasma levels. Coronary venous purines and catecholamines increased transiently. Two hours after reperfusion, heart rate was elevated from the initial 87.5 +/- 6.3 to 126 +/- 6.4 beats/min (p less than 0.01) and the pressure-rate product (PRP, an index of oxygen demand) from 9,530 +/- 630 to 11,950 +/- 790 mm Hg/min (p less than 0.05). After 2 weeks, six surviving pigs had a decreased stroke volume (98 +/- 18 versus the initial 124 +/- 14 microliters/kg, p less than 0.05), a prolonged high-frequency signal-averaged QRS duration (81.2 +/- 6.5 versus 65.7 +/- 2.9 ms, initially; p less than 0.05), and ventricular tachycardias (VTs), inducible by programmed electrical stimulation (PES). After the infusion of isradipine (1 microgram/kg/min for 30 min), the cardiac index increased from 92 +/- 14 to 133 +/- 8.7 ml/min.kg (p less than 0.02). Even at a higher heart rate, the PRP dropped from 12,600 +/- 1,900 to 10,560 +/- 1,400 mm Hg/min (p less than 0.05). Sustained monomorphic tachycardias were inducible in five pigs before and in three pigs after isradipine, and no deterioration of the signal-averaged electrocardiogram parameters was found.(ABSTRACT TRUNCATED AT 250 WORDS)

The converting enzyme not only converts angiotensin I into angiotensin II but also metabolizes bradykinin. Furthermore, the effects of ischemia on myocardial tissue damage can be modulated by converting enzyme inhibitors. It is unknown whether these effects of ACE-inhibitors are due to increased bradykinin production. In this paper we describe the effects of captopril on bradykinin production in the ischemic isolated rat heart. The reduced deleterious effects of ischemia by captopril were associated with a stimulated bradykinin production. Beneficial effects of bradykinin could be due to an improved perfusion or to an effect on cellular metabolism. Therefore, we conclude that this effect on kinins by ACE-inhibitors is of importance in modulating tissue damage during ischemia.

Since angiotensin converting enzyme (ACE) metabolizes bradykinin, the hypotensive effect of ACE inhibitors could be partly due to an increased bradykinin activity. We therefore investigated the influence of HOE K86-4321 [D-Arg-(Hyp2-Thi5,8-DPhe7)-bradykinin], a selective bradykinin-2 receptor antagonist, on the effects of enalaprilat (0.3 and 3.0 mg/kg) and zofenoprilat (0.1 and 1.0 mg/kg) on the heart rate, mean arterial blood pressure, cardiac output and total peripheral resistance in rats. Both enalaprilat and zofenoprilat reduced mean arterial pressure (from 110 +/- 7 to 85 +/- 6 and from 108 +/- 9 to 72 +/- 9 mmHg, respectively; P less than 0.05) and total peripheral resistance (from 515 +/- 35 to 413 +/- 29 and from 495 +/- 45 to 310 +/- 25 x 10(-3) mmHg/litre per min per kg, respectively; P less than 0.05); the heart rate and cardiac output changed little. In the presence of HOE K86-4321, which by itself did not affect the haemodynamic variables measured, the effects of the two ACE inhibitors were significantly reduced. These results suggest that bradykinin-2 receptor-mediated vasodilation, although not involved in blood pressure regulation, influences the reduction in blood pressure induced by enalaprilat and zofenoprilat in normotensive rats. Furthermore, at comparable ACE-inhibiting doses, zofenoprilat was more effective in reducing mean arterial pressure, which might be related to the presence of a sulphydryl group.