Effects of verapamil on pulmonary haemodynamics during hypoxaemia, at rest, and during exercise in patients with chronic obstructive pulmonary disease.

Abstract

The haemodynamic effects of intravenous verapamil at rest, during hypoxaemia, and during progressive exercise were evaluated in 10 patients with chronic obstructive lung disease. Verapamil produced significant decreases in the peak heart rate and systemic blood pressure during exercise but exercise capacity and pulmonary gas exchange at exhaustion were unaffected. There were no significant changes in pulmonary artery pressure or total pulmonary vascular resistance during exercise or during the breathing of either air or a hypoxic gas mixture at rest. No clinically useful benefit was found with verapamil in the dosage used in this group of patients and the value of calcium antagonists in the treatment of patients with chronic obstructive lung disease requires further clarification. chronic bronchitis and emphysema were included. Patients with known left ventricular disease and those taking beta adrenergic blocking agents, antiarrhythmics, or digitalis were excluded. All patients were taking long acting theophylline compounds and nebulised metaproterenol. These agents were last administered about one hour before the study began. Study protocol Catheters were placed in the radial and pulmonary arteries. Mean pulmonary artery pressure (PAP) was measured with patients seated breathing room air and the measurements were repeated while they breathed a hypoxic gas mixture. sGaw (s-' cmH2O-1) 0-06 (0-03) 0-03-0-13 FVC-forced vital capacity; TLco-diffusing capacity (transfer factor); TLC-total lung capacity; FRC-functional residual capacity; RV-residual volume; sGaw-specific conductance (conversion to s-kPa-I x 10).

Effects of Nifedipine on Diffusing Capacity and Pulmonary Capillary Blood Volume in Chronic Obstructive Pulmonary Disease

“…The effects of nifedipine on systemic arterial pres sure and heart rate in the present study are similar to previous reports [7,9,20]. Nifedipine decreased sys temic arterial pressure at both doses (significantly on ly for 20 mg).…”

“…The acute beneficial effect of nifedipine on HPV disappeared 2 months after the start of nife dipine treatment [18]. As a result of the reversal of hy poxic HPV and increased perfusion of hypovcntilated lung regions, nifedipine produced a decrease in P a02, except when subjects exercised in room air [7], On the contrary, some reports have shown that a vasodilata tor can either improve (hydralazine) [19] or cause no change (verapamil) [20] in the gas exchange. The changes in Pa02 observed in COPD patients with vasodilatator administration are difficult to interpret because of the possible multiple sites of action: car diac output, ventilation, ventilation-perfusion rela tionship, oxygen uptake and increased sympathetic nerve traffic due to systemic hypotension.…”

Hypoxia Inducible Factor 1 Mediates Hypoxia-Induced TRPC Expression and Elevated Intracellular Ca 2+ in Pulmonary Arterial Smooth Muscle Cells

“…Because PASMCs from chronically hypoxic animals are depolarized, presumably secondary to decreased voltage-gated K ϩ channel activity, 8 -10 it was hypothesized that an increase in [Ca 2ϩ ] i attributable to activation of voltage-dependent Ca 2ϩ channels (VDCCs) is the mechanism underlying hypoxic pulmonary hypertension. 9,10 This possibility was contradicted, however, by data indicating that VDCC antagonists did not prevent development of hypertension secondary to CH 4,11,12 and that acute administration of vasodilators, 3 but not VDCC antagonists, 11,13 reduced pulmonary artery pressure in patients with hypoxic pulmonary hypertension. Furthermore, we demonstrated that removal of extracellular Ca 2ϩ , but not VDCC blockers, decreased [Ca 2ϩ ] i during CH, 7 indicating a role for Ca 2ϩ influx through pathways other than VDCCs.…”

Pulmonary Vascular and Ventricular Dysfunction in the Susceptible Patient (2015 Grover Conference Series)

“…Given that initial experiments detailing the hypoxia-induced structural changes in the pulmonary circulation revealed thickening of the medial layer due to increased smooth muscle and fibroblast proliferation and that acute exposure to O 2 , calcium channel blockers, or other vasodilators had little effect on P PA , [30][31][32][33] it was widely regarded that contraction played a minimal role in sustained HPH and that "fixed" remodeling was the underlying cause of the increased PVR. This assertion was challenged, however, by striking studies demonstrating that inhibitors of Rho kinase (ROCK), an important mediator of smooth muscle cell contractility, acutely normalized P PA in chronically hypoxic rats when administered systemically 34,35 or via inhalation, 36 indicating that active contraction may, in fact, be the most important factor determining P PA .…”