The effect of verapamil on myocardial exchange of free fatty acids, citrate, lactate and glucose in coronary artery disease

Twelve patients with coronary artery stenosis (> 50% diameterreduction) underwent two identical periods of atrial pacingbefore and after i. v. verapamil (0.1 mg/kg). Myocardial exchangesof free fatty acids (FFA), citrate, lactate and glucose wereevaluated from measurements of arterio-coronary sinus differences(n = 12) and coronary sinus blood flow (CSBF) (n = 9). Beforeverapamil 11 patients developed angina. Verapamil abolishedpain in seven and improved pacing time to angina in four patients.After verapamil, aortic pressure decreased (P < 0.05), whilethe rate pressure product remained unchanged during rest andpacing. Verapamil decreased CSBF by 20% (P<0.05) during pacing,and increased oxygen extraction both during pacing and recovery.During pacing verapamil increased net FFA extraction (P<0.01)and uptake (1 to 8 µmol/min P<0.05), and decreasedglucose extraction (P<0.05) and uptake (22 to 11 µmol/min P< 0.02. Verapamil increased myocardial citrate releaseduring pacing (P < 0.05), suggesting a citrate inhibitionof glycolysis as a possible mechanism of the inhibited glucoseuptake. During pacing, verapamil reduced lactate release inseven patients (P<0.05) and decreased lactate extractionin five patients (P<0.05). The results suggest that verapamilmediates its beneficial effect on pacing-induced angina, inpart by changing substrate utilization of the ischaemic myocardiumin man towards that of normal heart.     

Retraction of a Malfunctioning Cardiac Bioptome from the Heart

A cardiac bioptome with persistent open jaws due to malfunction was removed from the cardiac cavity after the bioptome covering had been peeled off and a fractured wire identified and manipulated.     

Vasospastic Ischaemia Induced by the Hyperventilation Test in Patients with a Negative Response to Ergometrine

ABSTRACT. We present the case histories of two patients with angina pectoris who developed coronary artery spasm in response to provocation with prolonged hyperventilation (verified by ST segment elevation in both and coronary angiography in one) despite a negative ECG response to intravenous injection of 0.4 mg ergometrine. This new observation, which is in conflict with recent publications stating that ergot provocation is more sensitive than hyperventilation, suggests that in some patients diagnostic provocation with hyperventilation may be an alternative to the widely used ergot provocation.     

Autonomic balance in patients with angina and a normal coronary angiogram

The pathophysiology of angina pectoris in patients with a normalcoronary angiogram is not clear. Furthermore, the pathophysiologicalimpact of ST changes in syndrome X is controversial. The purposeof this study was to investigate cardiac autonomic function,by measuring 24 h heart rate variability, in patients with andwithout electrocardiographic evidence of ischaemia during exercise. Thirty-two patients with angina pectoris, a normal coronaryangiogram, echocardiogram, hyperventilation test and gastro-oesophagealinvestigation were studied. Fourteen healthy subjects servedas controls. Fifteen patients had significant ST segment depressionduring stress testing, whereas 17 had no electrocardiographicsigns of ischaemia. Heart rate variability was calculated as(1) mean RR= mean of all normal RR intervals, (2) the differencein mean RR level between when awake and when asleep (mean RRwake-sleep)—a tentative index of sympathetic activation,(3) the standard deviation (SD)—a broad band measure ofautonomic balance, and (4) a percentage of successive RR intervaldifferences 6% (pNN6%)—an index of vagal modulation. Thecoronary vascular resistance was measured at rest and duringpacing. Mean RR and autonomic indexes did not differ between patientswith a positive exercise test and controls (831/884 m 24 h SD125/134 m pNN6% 6.715.4%, respectively). Patients with a normalexercise test had shorter mean RR (758 ms vs 844 m P<0.05)and significantly reduced 24-h SD (103 ms vs 134 m P<0.05)than controls, whereas values for vagal index (6.5% vs 5.4%)did not differ from healthy controls. Mean RR wake-sleep alsotended to be lower in patients with a normal exercise test (–125 ms vs – 173 ms) compared to controls (P<0.1). Patientswith a positive exercise test had a significantly attenuatedreduction in coronary vascular resistance during pacing in comparisonto patients with a normal exercise test (–0.131–0.26mmHg x min. ml^{– 1}; P<0.05). The findings suggest the occurrence of general elevated sympatheticactivation in angina patients with a normal exercise test. Patientswith a positive exercise test exhibited no signs of autonomicdysfunction although these patients had altered coronary vascularresistance indicating microvascular angina. This supports thesuggestion that patients with a normal exercise test constitutean independent pathophysiological entity.     

Impaired human coronary artery distensibility by atherosclerotic lesions: a mechanical and histological investigation

The objective of this study was to evaluate the relationship between human coronary artery distensibility and vessel wall morphology assessed by histomorphometry. Coronary artery pressure-cross-sectional area relations and distensibility were studied in excised autopsy hearts by means of a balloon-based impedance planimetric technique 2 cm from the aortic orifice of the arteries. Later the hearts were perfusion fixed at 100 mm Hg and cross-sectioned 17, 20 and 23 mm distal to the aortic orifice. The areas of lumen, intima and media were measured. Nineteen left anterior descending coronary arteries (LAD) and 15 right coronary arteries (RCA) from 25 hearts (12 women and 13 men) were investigated. The age of the subjects was 48–97 years (mean 73.8 years). Non-linear relations were found between balloon pressure and coronary cross-sectional area (according with the function y = a + bx^0.5) and between balloon pressure and coronary distensibility, but there were no differences in these relations between the LAD and RCA. Subjects'' age was positively correlated with wall thickness (r = 0.44, P < 0.05), intima area (r = 0.46, P < 0.01) and media area (r = 0.44, P < 0.05) of the coronary arteries. Additionally, the distensibility at low pressures was inversely correlated with arterial wall thickness (r = −0.37, P < 0.05). When focusing only on arteries with concentric atherosclerotic lesions, distensibility at low pressures was inversely correlated with arterial wall thickness (r = −0.57, P = 0.01) and intima area (r = −0.53, P < 0.05). Arteries with concentric lesions were less distensible at low pressures compared with arteries having eccentric lesions (5.4 ± 0.8.10⁻²vs. 3.6 ± 0.7.10⁻² kPa⁻¹, P < 0.05) but this difference was absent at higher pressures. No difference in coronary artery distensibility was found between men and women. Age and distensibility were not correlated. These findings may have in vivo implications for complications to angioplasty procedures such as recoil and restenosis.     

Dose-related haemodynamic effects of nicardipine during rest and exercise and variable anti-anginal effects in patients with chronic stable angina

The effects of increasing doses ofi.v. nicardipine (2.5, 5.0and 7.5 or 10.0 mg) on blood pressure, heart rate and exerciseperformance were studied in 12 patients with chronic effortangina. Plasma nicardipine concentrations correlated closelywith the infused doses (r=0.90). Resting haemodynamic changesafter nicardipine included a dose-related fall in systolic (5%,13%, 15%) anddiastolic (0%, 6%, 8%) blood pressure and a risein heart rate (10%, 19%, 30%). Rate-pressure product was slightlyincreased after the highest dose (10%). During exercise, maximalsystolic blood pressure decreased (3%, 9%, 9%) and heart rateincreased (2%, 4%, 9%) but the rate-pressure product remainedunchanged. Exercise tolerance improved in 10 patients as indicated by prolongedexercise duration in all, delayed appearance of ST-segment depressionin 6, decreased maximal ST-segment depression in 5, and abolished(N = 3) or diminished (N=4) anginal pain at the end of exerciseafter optimal nicardipine dose. Five of the 10 patients obtainedmaximum benefit after the highest dose. The other five patientsimproved after 2.5 or 5.0 mg but deteriorated (N=4) or had nofurther benefit when the dose was increased (N= 1). One patientdeteriorated even after the lowest dose, whereas one patientneither improved nor deteriorated after any dose. The patientswho deteriorated after low or high doses tended to be more severelydiseased than those who tolerated the maximal dose well. Theresults stress the importance of individual dose titration ofnicardipine to ensure maximum benefit in patients with chroniceffort angina.     

Elevated level of erythropoietin in congestive heart failure Relationship to renal perfusion and plasma renin

Abstract. Background. In animal experiments reduction of renal perfusion can stimulate erythropoietin production. The relationship between renal haemodynamics and erythropoietin production is unknown in congestive heart failure. Objective. The aim was to study the relationship between serum erythropoietin and renal haemodynamics, plasma renin activity and haematocrit in patients with congestive heart failure and in healthy control subjects. Patients and methods. Serum erythropoietin, renal plasma flow, glomerular filtration rate and plasma renin activity were determined in 14 patients with acyanotic congestive heart failure, and 36 healthy controls. Results. Serum erythropoietin was significantly elevated in congestive heart failure 26.6 U l^?1 (median) compared with controls 17.0 U l^?1 despite a normal haematocrit, and increased with the severity of congestive heart failure (New York Heart Association class II: 17 U l^?1 [n = 4]; class III: 30 U l^?1 [n = 5]; class IV: 45 U l^?1 [n = 5]). Significant inverse correlations between serum erythropoietin and renal plasma flow (r = ?0.60, P < 0.03), and between serum erythropoietin and glomerular filtration rate, were found in congestive heart failure but not in the control subjects. A significant positive correlation (r = 0.71, P < 0.03) was demonstrated between serum erythropoietin and plasma renin activity in congestive heart failure. Conclusion. A severe reduction in renal perfusion in congestive heart failure appears to cause an increase in serum erythropoietin.     

Exercise Stress Testing in Angina Patients with Positive Response to Hyperventilation Testing: Influence of the Coronary Artery Tone

ABSTRACT We studied the exercise stress test and the coronary artery tone in two groups of angina patients with comparable coronary atherosclerosis. Group I (20 males and 5 females, mean age 53.5 years) with a positive, and group 11 (22 males and 3 females, mean age 52.5 years) with a negative response to the hyperventilation test (HVT). A positive exercise stress test (ST depression ≥1 mm) was found in 24 patients in group 1 vs. 15 in group II (p<0.01), despite a lower maximal rate pressure product (198±11.2 vs. 236±10.1, p<0.05) and maximal work load (110 W±7.1 vs. 136±7.4 W, p<0.02) in group I. A high coronary artery tone (dilatation (DIL %) of the coronary arteries after nitroglycerin ≥ 10%) was found in 18 patients in group I and in 4 in group II (p<0.01). DIL % was 22.6±3.8 vs. 5.8±1.4 in groups I and II, respectively (p<0.005). DIL% was significantly related to persistence of ST depression after exercise (r=0.36, p<0.05), and 21 of 22 patients with high tone had a positive exercise stress test vs. 18 of 28 with low tone (p<0.05). These findings suggest that the coronary artery tone influences the response to exercise in some patients with angina. Since the patients in group I were identified by HVT, our results underline the clinical relevance of this test.