vasoactive-intestinal-peptide and Coronary-Disease

Low-frequency transcutaneous nerve stimulation (TNS) is known to produce widespread and prolonged vasodilation in skin and muscles. In the present study the effects of low-frequency TNS on coronary and systemic haemodynamics, myocardial blood flow, myocardial oxygen consumption, myocardial free fatty acid and lactate uptake were measured at rest in 16 normotensive patients, with coronary heart disease, undergoing diagnostic cardiac catheterization. In addition, vasoactive intestinal polypeptides (VIP) and noradrenaline were measured in the coronary sinus and the aorta. The study was randomized and double-blind, with half of the patients serving as placebo controls. A stimulation period of 20 min caused a significant lowering of mean femoral arterial pressure and systemic vascular resistance measured at 15 and 30 min after the start of TNS (P less than 0.01). There was no significant change in the other parameters mentioned. The hypotonic effect is considered to be due to increased peripheral microcirculation resulting from sympatho-inhibition.

Topics: Coronary Circulation; Coronary Disease; Double-Blind Method; Fatty Acids, Nonesterified; Female; Hemodynamics; Humans; Lactates; Lactic Acid; Male; Middle Aged; Myocardium; Norepinephrine; Oxygen; Random Allocation; Transcutaneous Electric Nerve Stimulation; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP) is a systemic and coronary vasodilator that may have positive inotropic properties. Myocardial levels of VIP were assayed before and after the development of heart failure in two canine models. In the first, cobalt cardiomyopathy was induced in eight dogs; VIP (by radioimmunoassay) decreased from 35 +/- 11 pg/mg protein (mean +/- SD) to 5 +/- 4 pg/mg protein (P less than 0.05). In six dogs with doxorubicin-induced heart failure, VIP decreased from 31 +/- 7 to 11 +/- 4 pg/mg protein (P less than 0.05). In addition, VIP content of left ventricular muscle of resected failing hearts in 10 patients receiving a heart transplant was compared with the papillary muscles in 14 patients (five with rheumatic disease, nine with myxomatous degeneration) receiving mitral valve prostheses. The lowest myocardial VIP concentration was found in the hearts of patients with coronary disease (one patient receiving a transplant and three receiving mitral prostheses) (6.3 +/- 1.9 pg/mg protein). The other patients undergoing transplantation had an average ejection fraction of 17% +/- 6% and a VIP level of 8.8 +/- 3.9 pg/mg protein. The hearts without coronary artery disease (average ejection fraction of this group 62% +/- 10%) had a VIP concentration of 14.1 +/- 7.9 pg/mg protein, and this was greater than in hearts of the patients with coronary disease and the hearts of patients receiving a transplant (P less than 0.05). Myocardial catecholamines were also determined in 14 subjects; a weak correlation (r = 0.57, P less than 0.05) between the tissue concentrations of VIP and norepinephrine was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Animals; Cobalt; Coronary Disease; Disease Models, Animal; Dogs; Doxorubicin; Female; Heart Diseases; Humans; Male; Middle Aged; Myocardium; Norepinephrine; Stroke Volume; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide, a neurotransmitter peptide detected in animal and human hearts, has been found in nerves of coronary arteries. To determine the amount and distribution of vasoactive intestinal polypeptide in the large coronary vessels and its possible participation in coronary vasoregulation, two groups of animals were studied. In the first group, 11 anesthetized dogs were sacrificed to collect three (1 cm) segments along the circumflex and left anterior descending coronary arteries. These segments represented proximal (I), middle (II) and distal (III) portions of the two arteries. Concentrations (ng/g) of vasoactive intestinal polypeptide-like immunoreactive substance were determined by radioimmunoassay. Vasoactive intestinal polypeptide-like immunoreactivity was present in the left anterior descending (I = 7.28 +/- 1.65, II = 3.74 +/- 0.57, III = 2.29 +/- 0.53) and circumflex (I = 4.16 +/- 1.52, II = 4.58 +/- 1.13, III = 4.00 +/- 0.81) coronary arteries. The difference in vasoactive intestinal polypeptide-like immunoreactivity among epicardial segments of the anterior descending artery was significant, but there was no significant difference among segments of the circumflex coronary artery. In the second group (eight closed chest anesthetized dogs), the effects of vasoactive intestinal polypeptide intracoronary infusion on epicardial coronary constriction were examined at rest and with the artery constricted by serotonin. Left anterior descending (segments I, II and III) artery responses (% area change) to vasoactive intestinal polypeptide and vasoactive intestinal polypeptide plus serotonin were examined using quantitative coronary angiography. Vasoactive intestinal polypeptide infusion resulted in significant vasodilation in all the segments (I, II and III) of the left anterior descending artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aorta; Cardiac Catheterization; Coronary Circulation; Coronary Disease; Coronary Vessels; Dogs; Hemodynamics; Infusions, Intra-Arterial; Myocardium; Radioimmunoassay; Serotonin; Vasoactive Intestinal Peptide

We evaluated the effects of ischemic injury on the myocardial adenylate cyclase system, 5 h after ligation of the left anterior descending coronary in 5 anesthetized dogs. Crude cardiac membrane preparations were isolated from control and ischemic areas of ventricular myocardium and tested for: 1. L-(125I)iodocyanopindolol binding, in the absence and presence of +/- -isoprenaline and GTP, and 2. adenylate cyclase activity. The density of beta-adrenoceptors increased by 35% in membranes from ischemic areas while the proportion of receptors in a high affinity state for +/- -isoprenaline decreased from 43% to 20%. Adenylate cyclase activities in the basal state and under stimulation with NaF, forskolin, Gpp(NH)p, +/- -isoprenaline and VIP were all markedly and similarly reduced, being only about 30% of comparable activities in membranes from control areas. The +/- -isoprenaline subsensitivity of cardiac adenylate cyclase can, thus, be attributed to a defective enzymatic system and not to a reduction in the number of beta-adrenoceptors implying that the internal components of the system were more sensitive to acute ischemia than the outward oriented hormone receptors. It is tempting to ascribe this uncoupling to a functional depletion in the guanine nucleotide-binding regulatory protein Ns that might reflect a loss of high energy phosphate stores including GTP.

Topics: Adenylyl Cyclases; Animals; Binding, Competitive; Colforsin; Coronary Disease; Dogs; Guanosine Triphosphate; Guanylyl Imidodiphosphate; In Vitro Techniques; Isoproterenol; Male; Membranes; Myocardium; Receptors, Adrenergic, beta; Sodium Fluoride; Vasoactive Intestinal Peptide