Large coronary arteries undergo marked circumferential and axial deformations due to changes in blood pressure and gross movements of the ventricular wall during systole and diastole. The present study was designed to investigate 1) whether axial stretch of large coronary arteries influences the sensitivity to vasoconstrictors, 2) the mechanisms mediating stretch-dependent changes in vascular sensitivity. Endothelium-denuded cylindrical segments from large porcine coronary arteries were studied under isometric conditions using a balloon-based impedance planimetric technique. In segments subjected to a pressure of 60 mmHg, 20% axial stretch caused a left-ward shift of the concentration-response curves for K+ and 5-hydroxytryptamine (5-HT). Enhancement of vascular sensitivity to 5-HT induced by axial stretch was observed also in maximally K+-depolarized coronary arteries. Protein kinase C inhibition by calphostin C (1 microM) slightly decreased the spontaneous resting tone at 60 mmHg and inhibited the leftward shift of the concentration-response curve for 5-HT elicited by axial stretch. These results suggest that axial stretch of the vessel wall enhances the sensitivity of coronary arteries to vasoconstrictors by a protein kinase C-dependent mechanism.

OBJECTIVE: To evaluate the role of nociception in patients with angina despite normal coronary angiograms and to investigate whether any abnormality is confined to visceral or somatosensory perception. METHODS: Perception, pain threshold, and brain evoked potentials to nociceptive electrical stimuli of the oesophageal mucosa and the sternal skin were investigated in 10 patients who had angina but normal coronary angiograms, no other signs of cardiac disease, and normal upper endoscopy. Controls were 10 healthy volunteers. The peaks of the evoked potential signal were designated N for negative deflections and P for positive. Numbers were given to the peaks in order of appearance after the stimulus. The peak to peak amplitudes (P1/N1, N1/P2) were measured in microV. RESULTS: (1) Angina pectoris was provoked in seven patients following continuous oesophageal stimulation. (2) Distant projection of pain occurred after continuous electrical stimulation of the oesophagus in four patients and in no controls. (3) Patients had higher oesophageal pain thresholds (median 16.3 mA v 7.3 mA, P = 0.02) to repeated stimuli than controls, whereas the values did not differ with respect to the skin. There were no intergroup differences in thresholds to single stimuli. (4) Patients had substantially reduced brain evoked potential amplitudes after both single oesophageal (P1/N1, median values: 7.2 microV, controls: 29.0 microV; N1/P2: 16.5 microV, controls: 66.0 microV; P < 0.001 for both) and skin (N1/P2: 13.5 microV; controls: 76.0 microV; P < 0.001) stimuli despite the similar pain thresholds. CONCLUSION: Central nervous system responses to visceral and somatosensory nociceptive input are altered in patients who have angina despite normal coronary angiograms.

Somatostatin is widely used in experimental metabolic studies to control hormone actions. It has also been suggested that, in addition to its well known suppressive effects, somatostatin per se may increase insulin sensitivity. In order to examine this suggestion, we gave six healthy male volunteers (age 33 +/- 1 yr, mean +/- SEM; body mass index, 24.1 +/- 0.6 kg/m2) either a local intraarterial (brachial artery) or a systemic venous infusion of 25 micrograms/h somatostatin twice. The study consisted of a 1-h basal period and a 2-h systemic hyperinsulinemic (0.4 mU/kg.min) euglycemic clamp. Compared with the systemic control infusion, local forearm perfusion with somatostatin caused a 55% increase in insulin-stimulated forearm glucose uptake (0.74 +/- 0.18 vs. 0.47 +/- 0.19 mmol/L, P < 0.05). Intraarterial somatostatin perfusion did not alter basal forearm glucose uptake (0.14 +/- 0.07 vs. 0.17 +/- 0.12 mmol/L), the amount of glucose administered during the clamp (M-value, 3.2 +/- 0.5 vs. 3.0 +/- 0.6 mg/kg.min), or the levels of insulin, C-peptide, glucagon, or GH. Intermediary metabolite exchange across the forearm, total forearm blood flow, and oxygen saturations also remained stable. Glucose concentrations were slightly higher (0.06 +/- 0.01 mmol/L) in arterial than in arterialized blood, whereas lactate concentrations were comparatively decreased (108 +/- 51 mumol/L) in arterial blood. Our data suggest that somatostatin increases insulin-stimulated muscle utilization of glucose through local mechanisms. Although the nature of this increase remains to be established, it should be taken into consideration in metabolic studies using somatostatin.

After 10 mg nicardipine IV a patient with stable angina developed chest pain and ST-segment depression accompanied by excessive tachycardia, low arterial blood pressure, and initially decreased coronary sinus blood flow. Measurements of arterial concentrations and cardiac exchanges of lactate, glucose, free fatty acids, glutamate, and alanine showed alterations indicative of severe ischemia.

Ten patients with chronic effort angina and coronary artery disease (luminal diameter reduction greater than 75%) were stressed by atrial pacing (140 beats/minutes) before and 15 minutes after intravenous propranolol (mean dose 7.4 mg). Myocardial substrate exchange of oxygen, blood lactate, plasma free fatty acids, citrate, glucose, glutamate, and alanine as well as coronary sinus blood flow were measured. Coronary sinus blood flow, oxygen consumption, and systemic haemodynamics did not change after propranolol. Propranolol did not influence arterial lactate concentration, and it reduced the arterial concentration of free fatty acid by 37% and increased that of glutamate by 21%. During pacing myocardial lactate extraction increased in all 10 patients; in two lactate release was converted to lactate uptake. Propranolol reduced free fatty acid uptake and increased glutamate uptake during pacing. For both substances the changes in aortocoronary sinus differences or in uptake or both correlated positively with the changes in their delivery to the heart from extracardial sources (arterial concentrations/loads). In the unstressed state before pacing, aortocoronary sinus lactate differences correlated inversely with free fatty acid differences and positively with those of glutamate. During pacing the relation between lactate and glutamate differences remained positive while the inverse correlation between lactate and free fatty acid differences was lost. Myocardial citrate release was halved during pacing and recovery. Propranolol did not influence alanine or glucose exchanges. An improved myocardial lactate extraction after propranolol administration may be secondary to decreased free fatty acid uptake or increased glutamate uptake or both. In the unstressed state both mechanisms may be of importance. During pacing induced ischaemia, increased glutamate uptake is more likely than reduced free fatty acid uptake to be the mechanism responsible for the improvement in myocardial lactate extraction. The propranolol mediated alterations in myocardial substrate exchanges may reflect the extracardial effects of the drug.

Eighteen patients, 13 male and five female, with unstable angina pectoris and who had greater than or equal to 3 anginal attacks/day despite treatment with beta- and/or Ca-blockers were treated for three days with transdermal nitroglycerin (Transiderm-Nitro 25 mg/24 hours) in a randomised, placebo-controlled trial. A significant reduction of anginal attacks (p = 0.03) was demonstrated only during the first day of treatment. The lack of significant effects during the following two days was ascribed partly to the possible development of nitrate-tolerance, partly to a declining number of anginal attacks in the placebo-group during the trial period, for which reason the difference between the actively treated and the placebo group became smaller and finally the consumption of nicomorphine was considerably greater in the placebo group.

The effect of 30 mg sublingual nifedipine on cardiac metabolism and haemodynamics was studied during two identical periods of pacing in 11 patients with chronic coronary artery disease. The pace time to angina pectoris improved after nifedipine in 6 patients, deteriorated in 2 and was unchanged in 3. Nifedipine decreased blood pressure (12%), rate pressure product (10%) and coronary vascular resistance (17%) during pacing. Aorto-coronary sinus (A-Cs) oxygen difference decreased at rest (9%) and postpacing (10%) after nifedipine, although an opposite tendency in coronary sinus blood flow resulted in unchanged myocardial oxygen uptake throughout the study. Although mean myocardial lactate extraction after nifedipine was unchanged during pacing in the whole group of patients, it increased in 9 patients who showed a net lactate release at control pacing (from -50.9 +/- 33.5% to -35.9 +/- 30.2%, P less than 0.05). Nifedipine increased free fatty acid (FFA) extraction during pacing (from 1.5 +/- 12.9% to 17.4 +/- 13.1%, P less than 0.02) and uptake (from 1.8 +/- 8.5 to 11.1 +/- 10.6 mu mol min-1, P less than 0.05). Nifedipine influenced only glucose exchange significantly (46% decreased extraction) at 5 min postpacing. The A-Cs citrate gradient lessened 30-40% postpacing after nifedipine administration. Since the unloading effects of nifedipine did not alter myocardial oxygen uptake, the most important net haemodynamic finding was the decrease in coronary vascular resistance. Although no significant antianginal effect of a fixed dose of nifedipine was found, the increased uptake of FFA may reflect improved myocardial oxidative metabolism after nifedipine.