Control Of Systemic Hemodynamics Research Articles

Intra-arterial administration of verapamil for prevention and treatment of cerebral angiospasm after SAH due to cerebral aneurysm rupture

The study purpose was to analyze the efficacy of intra-arterial administration of verapamil (IAV) in the treatment of angiospasm in SAH patients and to determine optimal parameters of the procedure. A number of studies demonstrated the efficacy of intra-arterial administration of vasodilators, in particular verapamil, in the treatment of angiospasm after aneurysmal SAH, which served the basis for inclusion of this method in the recommended protocol for treatment of SAH patients [1-7]. We analyzed the efficacy of IAV in 35 patients in the acute period of SAH, with 77.2% of the patients having a Hunt-Hess score of III-V. The inclusion criteria were as follows: IAV within two weeks after SAH; excluded aneurysm; verapamil dose per administration of at least 15 mg; follow-up for at least three months. Efficacy endpoints were as follows: changes in spasm according to angiography and transcranial dopplerography (TCDG); development of ischemic lesions; clinical outcome according to the modified Rankin scale. A total of 76 IAV procedures were performed. The verapamil dose per procedure was 36.7±9.7 mg, on average; the number of procedures varied from 1 to 5. One arterial territory was treated in 12 cases, two arterial territories were treated in 48 cases, and three arterial territories were treated in 15 cases. Typical adverse reactions included decreased blood pressure, a reduced heart rate, and elevated ICP. In all cases, TCDG revealed signs of reduced angiospasm - a 20-40% decrease in the LBFV in the M1 MCA. Four (11.4%) patients died; of these, only one died due to angiospasm progression. On examination at 3 months or more after discharge, favorable outcomes were observed in 74.3% of cases. IAV is associated with a low risk of significant complications. IAV should be performed under control of systemic hemodynamics and ICP. The indications for IAV include signs of moderate worsening or severe angiospasm according to TCDG and/or angiography. The IAV procedure may be performed every day. Further clarification of the IAV procedure and evaluation of clinical outcomes under prospective study conditions are required.

Roles of central renin-angiotensin system and afferent renal nerve in the control of systemic hemodynamics in rats

Afferent renal nerves (ARNs) convey signals generated by physiological changes in the kidney to the central nervous system. The aim of this study was to determine whether ARNs contribute to cardiovascular regulation through central renin-angiotensin system (RAS)-dependent pathways. Blood pressure and renal sympathetic nerve activity (RSNA) were monitored during elevations in pelvic pressure in anesthetized Wistar-Kyoto Izm (WKY) rats and spontaneously hypertensive Izm rats (SHRs). In both groups of rats, blood pressure and RSNA were significantly increased in response to elevations in renal pelvic pressure in a pressure-dependent fashion, which were prevented by renal denervation. Injection of an angiotensin II type I receptor blocker (CV-11974, 10 μg) into the intracerebroventricular region significantly suppressed the vasopressor and sympathoexcitatory responses to the increases in pelvic pressure in both WKY rats and SHRs, although these inhibitory effects of CV-11974 in SHRs appeared to be weaker than in WKY rats. These results indicate that signals transmitted by ARNs have an important role in the control of systemic hemodynamics through regulating central RAS-mediated changes in sympathetic nerve activity.

Targeting Heme-Oxidized Soluble Guanylate Cyclase

Increased peripheral vascular resistance is a hallmark of advanced chronic congestive heart failure (CHF) and contributes to the phenomenon of increased afterload that complicates that condition. Multiple factors have been proposed to contribute to this phenomenon, such as increased sodium water content of the vasculature, increased activation of neurohormonal vasoconstrictor forces, and intrinsic abnormalities of the vasculature. During the past decade, it has also been shown that CHF is associated with a severe degree of endothelial dysfunction in experimental animals, as well as in humans. Given that the endothelium, as well as endothelium-dependent vasodilation, plays a crucial role in the control of systemic hemodynamics, this phenomenon is probably an important reason for increased vascular resistance and afterload in heart failure. Because the NO–cGMP–cGMP-dependent kinase-1 relaxation pathway is predominantly responsible for the regulation of vascular tone (Figure), numerous studies have examined abnormalities of this pathway in heart failure. Experimental and clinical studies revealed that NO production is decreased because of decreased expression of endothelial NO synthase and diminished endothelial NO synthase–mediated NO production. A further related mechanism related to this is increased production of vascular superoxide anions, which may react with NO in a diffusion-limited reaction to form the highly reactive intermediate peroxynitrite (Figure). Increased superoxide production, however, is clearly not limited to the endothelium, because more recent experimental studies revealed increased oxidative stress throughout the vasculature, including the media and adventitia.1 Oxidative stress within the media reacts with NO formed as it diffuses from the endothelium and also inhibits NO signaling, thereby causing a state of vascular NO resistance. Theoretically, the decrease in vascular NO bioavailability may be used as an argument to initiate …

Effects of intracoronary calcium chloride on the postischemic heart in pigs

Whether calcium chloride (CaCl2) should be used to reverse myocardial dysfunction during cardiac operations remains a controversial issue. Calcium chloride may reduce, rather than increase, myocardial contractility and may produce exaggerated vasoconstriction in postischemic vessels in which the endothelium has been damaged. These possibilities were investigated in an open-chest porcine model that allowed control of systemic hemodynamics. Incremental doses of CaCl2 (1, 3, and 10 mg/min) were infused directly into a coronary artery before and after 10 or 15 minutes of ischemia followed by 15 minutes of reperfusion. Calcium chloride increased regional contraction, coronary blood flow, and oxygen consumption before ischemia, whereas oxygen and lactate extraction were unchanged. After ischemia and reperfusion, contraction was impaired and lactate extraction was reduced, but a similar response to CaCl2 was observed. Contraction returned to baseline values promptly after CaCl2. Thus, CaCl2 exerts a positive inotropic effect both in normal and in postischemic myocardium. Calcium chloride does not cause direct coronary constriction nor does it worsen myocardial stunning after a short period of normothermic myocardial ischemia.

Effect of Verapamil on Regional Myocardial Contraction During Graded Ischemia in the Dog

Verapamil benefits patients with angina pectoris during exercise. The mechanism underlying this effect is controversial. A direct oxygen-sparing effect on ischemic myocardium has been proposed, but previous studies seeking to demonstrate this effect have been inconclusive because of inadequate control of systemic hemodynamics. This study has assessed the direct effects of verapamil on regional myocardial contraction during graded coronary flow reductions while blood pressure and heart rate were held constant. Verapamil caused a decrease in regional contraction at normal levels of coronary flow, a finding consistent with a negative inotropic effect. At lower coronary flows, however, ischemic dysfunction was similar in the presence and absence of verapamil. These findings fail to support the concept that verapamil either selectively depresses ischemic myocardium or enhances myocardial function during ischemia. Thus, these direct mechanisms would seem unlikely causes of the observed beneficial effect during exercise in patients with coronary artery disease.