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The effects of infusion of calcium and magnesium ions on the cardiovascular system in man.

The effects of Ca++ and Mg++ infusion on the cardiovascular system were studied in 96 normotensive subjects and 85 hypertensive patients. The results obtained were as follows: (1) The effects of Ca++ infusion on the systolic time intervals were characterized by the shortening of QS2I, PEPI, and ICT, and increase in ET/PEP. The responses of the systemic hemodynamics were elevation of mean blood pressure and increase in cardiac index and stroke index. The heart rate was not altered. (2) These results support that Ca++ has a positive inotropic action and increases the left ventricular performance. (3) The effects of Mg++ infusion on the systolic time intervals were characterized by the prolongation of QS2I, PEPI, and ECT. The responses of systemic hemodynamics were elevation of mean blood pressure and increase in heart rate. The ET/PEP and cardiac index tended to decrease, but these changes were not significant. (4) From these results it is suggested that Mg++ depress myocardial contractility and has a positive chronotropic action. (5) There were no significant differences in the systolic time intervals and hemodynamic responses to the infusion of Ca++ and Mg++ between normotensives and hypertensives.

Adolescent↗

Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs.

Neuropilin is a type 1 membrane protein, which is highly conserved among Xenopus frog, chicken and mouse. The extracellular part of the neuropilin protein is composed of three unique domains, each of which is thought to be involved in molecular and/or cellular interactions. In mice, neuropilin is expressed in the cardiovascular system, nervous system and limbs at particular developmental stages. To clarify the roles of neuropilin in morphogenesis in vivo, we generated mouse embryonic stem (ES) cell clones that constitutively expressed exogenous neuropilin, then produced chimeras using these ES cell clones. The chimeras overexpressed neuropilin and were embryonic lethal. The chimeric embryos exhibited several morphological abnormalities; excess capillaries and blood vessels, dilation of blood vessels, malformed hearts, ectopic sprouting and defasciculation of nerve fibers, and extra digits. All of these abnormalities occurred in the organs in which neuropilin is expressed in normal development. The variety of abnormalities occurring in these chimeric embryos suggested diverse functions of neuropilin in embryonic morphogenesis, which may be ascribed to multiple interaction domains identified in the molecule. Correct spatiotemporal expression of neuropilin seems to be essential for normal development of the cardiovascular system, nervous system and limbs.

Animals↗

The role of nitric oxide in regulation of the cardiovascular system in reptiles.

The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and inhibition of nitric oxide synthase (NOS) by l-nitroarginine methyl ester (l-NAME). Furthermore, preliminary data on the effects of SNP on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from our laboratory on three other species of reptiles: pythons (), rattlesnakes () and turtles (). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies on reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast, the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity.

Animals↗

Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system.

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system were examined. When PACAP-38 (270 or 420 pmol/kg body weight) was administered intravenously to the anesthetized dogs, both mean arterial pressure and left ventricular systolic pressure increased within 2 min after a temporal depression. Pulmonary arterial systolic pressure increased promptly. These hemodynamic values and heart rates (HR) 5 min after injection were significantly higher than the corresponding values in physiological saline injected dogs, and some effects were still sustained over 15 min. Cardiac output and stroke volume also increased and the values at 5 min were significantly higher than those in controls. The high dose of PACAP-38 (420 pmol/kg) evoked greater responses than those induced by the low dose (270 pmol/kg). Plasma adrenaline, but neither noradrenaline nor dopamine concentration significantly increased 15 min after injection of 420 pmol/kg PACAP-38. Moreover, PACAP-38 clearly stimulated cyclic AMP production in rat cardiac myocytes with EC50 of 1.5 x 10(-9) M and plasma cAMP levels significantly and dose-dependently increased in dogs 5 min after administration. These results first demonstrated that PACAP has inotropic and chronotropic actions on the heart possibly by a direct stimulation of adenylate cyclase in cardiac myocytes and also that the cardiovascular functions may be possibly modified by an evoked adrenaline secretion in vivo.

Animals↗

[Complications associated with nonfunctioning pacemaker electrodes retained within the cardiovascular system].

INTRODUCTION AND OBJECTIVE: The aim of the present study was to evaluate the complications in patients with functionless pacing leads retained in the cardiovascular system. PATIENTS AND METHODS: We retrospectively studied 39 patients: 31 underwent surgery for electrical or mechanical failure (group I) and eight for cutaneous pocket infection (group II). The follow-up was 45 +/- 34 months. RESULTS: Only one patient (3%) from group I presented infectious complications probably related to the retained pacing lead. Seven patients (87%) in group II presented recurrence of the infection with persistent fever and/or septicemia due to skin erosion and unnoticed pacing lead infection (p < 0.0005). Removal of the infected generator was performed in 8/39 (21%) of the patients. Thoracotomy to explant the infected retained leads was required in five of them (62%). No patient presented lead migration or venous thrombosis during the follow-up. CONCLUSIONS: Retained pacing leads in the cardiovascular system are well tolerated. However, in spite of adequate antibiotic treatment, patients with local and pacemaker system infection may present recurrence of the infection with persistent fever and/or septicemia. Early surgical pacemaker system removal is recommended in these patients due to the high morbidity.

Adult↗

Mathematical modeling of human cardiovascular system for simulation of orthostatic response.

This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

Blood Pressure↗

[Prostaglandins and the cardiovascular system].

Prostaglandins have been known for a long time to have a vaso-active action. The recent discovery that prostacycline or thromboxane A2 have a greater vascular action than the prostaglandins suggests that these substances may have a physiological or pathological role, for example in endotoxin shock, anaphylaxis, coronary thrombosis, chronic hypertension, etc. The discovery of the leukotrienes and their potent biological action of the cardiac rhythm reveals the importance of arachidonic acid metabolism, and therefore the fatty acids, in the cardiovascular system. This complex and as yet poorly understood metabolism offers a variety of options for pharmacological intervention. New approaches to drug treatment are being developed which may result in new treatment strategies in the years to come, thanks to the improved understanding of the biological role of prostaglandins, thromboxane and the leukotrienes in the cardiovascular system.

Animals↗

Interactions of adrenaline and magnesium on the cardiovascular system of the baboon.

Cardiovascular variables were measured in baboons before and during an adrenaline infusion at 1 microgram/kg/min, and following two bolus injections of either MgSO4 60 mg/kg or saline. Arterial blood pressure (ABP), systemic vascular resistance (SVR), central venous pressure (CVP), pulmonary arterial pressure and pulmonary capillary wedge pressure were all elevated by the adrenaline infusion. Cardiac output (CO), stroke volume (SV) and heart rate were unchanged but multifocal arrhythmias occurred. Mg infusion abolished arrhythmias and markedly increased CO and SV. SVR was reduced below baseline values by Mg, and ABP and CVP returned toward baseline. Saline did not alter adrenaline-induced changes in any way. It is concluded that Mg has powerful antiarrhythmic effects in the presence of catecholamines and, in addition, may have useful alpha-adrenergic antagonist effects.

Animals↗

The cardiovascular system after scorpion envenomation. A review.

Scorpion envenomation is a common medical problem and life hazard in many countries of the world. Scientific investigations have addressed the interrelationship between the stimulatory effects of the venom on the autonomic nervous system and adrenals and the subsequent effects of released transmitters on the cardiovascular system. A number of clinical cardiovascular syndromes may dominate the initial clinical presentation after envenomation: the syndromes usually vary with the age of the victim, the size of the offender and the season. Central nervous system dysfunction is seen in children but rarely observed in adults; if accompanied by severe hypertension the clinical picture is consistent with acute hypertensive encephalopathy. Heart failure, pulmonary edema or a shock-like syndrome has been observed in 25% and hypertension in 30% to 77% of our patients. The electrocardiographic abnormalities recorded in the majority of the patients after envenomation include an "acute myocardial infarction-like pattern." Rhythm disturbances are frequent but conduction abnormalities are rare. Echocardiographic, radionuclide and experimental hemodynamic observations have provided evidence that heart failure and pulmonary edema after envenomation are multifactorial with diminished systolic performance following the initially increased left ventricular contractility and decreased ventricular diastolic compliance. Clinical laboratory data reporting increased catecholamine metabolite excretion and elevated plasma renin and aldosterone are consistent with the stimulatory effects of the venom on the autonomic nervous system. Treatment, including our experience with vasodilators and calcium channel blockers, is reviewed.

Angiography↗

Regulation of corticotropin-releasing factor receptor type 2 beta messenger ribonucleic acid in the rat cardiovascular system by urocortin, glucocorticoids, and cytokines.

CRF receptor type 2 (CRF R2) messenger RNA (mRNA) expression in the rodent heart is modulated by exposure to both the bacterial endotoxin lipopolysaccharide (LPS) and glucocorticoids. In this study we examined the roles of glucocorticoids, cytokines, and CRF R2beta ligands in the regulation of CRF R2beta expression in the cardiovascular system both in vivo and in vitro. Using ribonuclease protection assays, we found that, in addition to the injection of LPS or corticosterone, physical restraint caused a decrease in CRF R2beta mRNA levels in the rat heart and aorta. Adrenalectomy with corticosterone replacement at constant levels partially blocked LPS-induced decreases in CRF R2beta mRNA expression in the heart. Thus, elevations of endogenous circulating corticosterone could contribute to the down-regulation of CRF R2beta mRNA expression in heart. To identify other putative modulating factors, we examined CRF R2beta expression in the aorta-derived A7R5 cell line. Incubation with CRF R2 ligands or dexamethasone reduced CRF R2beta mRNA levels. In addition, incubation with a variety of cytokines, proteins released during immune challenge, also reduced CRF R2beta mRNA expression. The multifactorial regulation of CRF R2beta mRNA expression in the cardiovascular system may serve to limit the inotropic and chronotropic effects of CRF R2 agonists such as urocortin during prolonged physical or immune challenge.

Adrenocorticotropic Hormone↗

Comparison of some effects of paroxetine with amitriptyline on the cardiovascular system in animals.

The effects of intravenous infusions of paroxetine, a novel inhibitor of 5-hydroxytryptamine (5HT) uptake, and of the tricyclic antidepressant, amitriptyline, on the cardiovascular system have been compared in the conscious rabbit and in the anaesthetised cat. As judged by the dose required to produce changes in ECG waveform (including PR and QTc intervals) and disorders of heart rhythm, paroxetine was less cardiotoxic than amitriptyline in both species. Thus, paroxetine has the advantage over amitriptyline of being less toxic to the cardiovascular system which could constitute a considerable advantage in clinical use particularly as other work has shown it to be more potent than amitriptyline in tests for antidepressant activity.

Amitriptyline↗

Chronic inhalation of carbon monoxide: effects on the respiratory and cardiovascular system at doses corresponding to tobacco smoking.

Carbon monoxide (CO) is a dangerous poison in high concentrations, but the long-term effects of low doses of CO, as in the gaseous component of tobacco smoke, are not well known. The aims of our study were to evaluate the long-term effects of inhaled CO on the respiratory and cardiovascular system at doses corresponding to tobacco smoking and its effect on tumourigenesis and pulmonary neuroendocrine (NE) cells. Female Wistar rats were exposed to either CO (200 ppm) for 20 h/day (n=51) or air (n=26) for 72 weeks. Carboxyhaemoglobin was 14.7+/-0.3% in CO exposed animals and 0.3+/-0.1% in controls. In the lungs, no signs of pathology similar to that associated with cigarette smoking were observed, and no differences in number of pulmonary NE cells were observed between the groups. Chronic CO inhalation induced a 20% weight increase of the right ventricle (p=0.001) and a 14% weight increase of the left ventricle and interventricular septum (p<0.001). Histological examination of the myocardium did not reveal any signs of scarring. In the aorta and femoral artery, no signs of atherosclerosis were observed in CO exposed rats. No exposure related carcinogenic effects were observed. Spontaneous tumours were identified in 29% of CO exposed animals and in 28% of the controls. Our results suggest that low dose CO exposure is probably not responsible for the respiratory pathology associated with tobacco smoking. The effects on the cardiovascular system seem to involve myocardial hypertrophy, but not atherogenesis.

Animals↗