Improved cardiac performance with human calcitonin gene related peptide in patients with congestive heart failure

Abstract

Study objective -The aim of the study was to assess the cardiovascular effects of human calcitonin gene related peptide (CGRP) in patients with congestive heart failure.Design -The effects of CGRP I1 (or p), 12.5 pgh-', given by intravenous infusion for 24 h to digitalised patients with congestive heart failure, were assessed by measurement of cardiac functional indices.Patients -Five patients (four female) were studied. Age was 73-82 years. Three were in New York Heart Association phase I11 and two in phase IV.Measurements and main results -The pre-ejection period to left ventricular ejection time ratio and the Q T distance adjusted for heart rate were lowered by 21% and 4% respectively. The left ventricular shortening index was raised by 43%. The arterial pressure and heart rate did not change consistently.Conclusion -Calcitonin gene related peptide improves myocardial contractility in patients with congestive heart failure. This is the first time this has been shown. vasodilatation, and hyp~tension.*-~ The stimulation of the heart rate and coronary vasodilatation presumably depend on the local release of CGRP from afferent nerve fibres in the heart induced by capsaicin and interaction with receptors linked to cyclic adenosine monophosphate The improved ventricular contractility of CGRP was suppressed in normal human subjects through blockade of adrenergic receptors, and may be driven by reflex sympathetic ~timulation.~ Here we show evidence of improved ventricular contractility with CGRP as recorded with non-invasive techiques in five digitalised patients with congestive heart failure. MethodsWe studied four female and one male patient aged 73 to 82 years with congestive heart failure, three in New York Heart Association phase I11 and two in phase IV. Four patients had coronary artery disease and the fifth had hypertrophic cardiomyopathy. Body weight was 44-66 kg, and height 147-158 cm. Informed consent about the experimental treatment with CGRP was obtained from all patients, and the study was approved by the appropriate ethics committee.The patients were treated with oral P-methyldigoxin (Lanitop, Boehringer, Mannheim, W Germany), 0.6 mg (0.77 nmol) per day for three days, followed by 0.3 mg (0.39 nmol) per day for four days (figure), after which they were given human CGRP I1 (or P) (Peninsula Laboratories, Belmont, CAY USA), 12.5 pgeh-' (3.3 nmol) by intravenous minipump infusion for 24 h.The systemic arterial pressure was monitored continuously by intra-arterial manometry. The duration of the pre-ejection period and the left ventricular ejection time were determined using electrocardiography, phonocardiography, and external carotid pulse tracings. l8 The corrected QT interval (QTJ was calculated by dividing QT by the square root of the preceding R-R interval. The left ventricular cavity was measured before and during the infusions with CGRP by M mode echocardiography at the end diastolic and the end systolic filling times." The left ventricular shortening index was calculated as the ratio between...

Positive inotropic and lusitropic effects of HNO/NO − in failing hearts: Independence from β-adrenergic signaling

“…This finding corroborates prior studies (10) and further clarifies differential effects between HNO͞NO Ϫ and NO donors (33)(34)(35). CGRP has positive inotropic activity involving enhanced calcium release (36) and is active in failing human hearts (37). The similar elevation in arterial, venous, and coronary sinus blood from AS in the present study precludes identification of the primary source (e.g., perivascular and organ-specific neurons).…”

The vanilloid receptor and hypertension1

“…Other studies have shown that CGRP has potential beneficial hemodynamic effects in congestive heart failure [79][80] . Shekhar et al observed that CGRP infusion over 8 h increased cardiac output by 72% while reducing right atrial and pulmonary wedge pressure [80] .…”

Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials

“…The number of patients studied so far, however, is inadequate for a definitive conclusion on the therapeutic value of exogenous CGRP in congestive cardiac failure. In patients with severe chronic congestive cardiac failure (New York Heart Association class III and FV, ejection fraction < 35%), short-term or prolonged infusions of CGRP showed beneficial effects (258). An 8-h infusion of CGRP to nine patients caused a 28% and 22% decrease in right atrial and pulmonary artery wedge pressure, and cardiac output was increased by 72%.…”