Cardiovascular parameters

FIGURE 10-1. Hemodynamic relationships between key cardiovascular parameters (panel A). Solid lines represent a direct relationship the broken line represents an inverse relationship. In panel B, the perturbations typically observed in hypovolemic shock are highlighted in blue with arrows depicting the likely direction of the pertubation. (Reprinted from Braunwald E. Regulation of the circulation. I. N Engl J Med 1974,290 1129, with permission.)... 

Initial safety tests were carried out in beagle dogs and subsequently in cynomolgus monkeys. Single bolus i.v. doses of up to 100 mg kg-1 were used and were found to exert no negative effect upon general condition, blood pressure, heart or cardiovascular parameters, respiration rate or body temperature. No safety tests evaluating potential product effects upon the central nervous system were undertaken, as the protein is considered unlikely to cross the blood-brain barrier. 

As described above, ondansetron has potent and highly selective antagonist properties at the 5-HT3-receptor [7]. The selectivity of action of ondansetron for the 5-HT3 receptor has been demonstrated using a number of in vitro preparations which respond to activation of a number of different neurotransmitter receptors. The selectivity ratio for ondansetron on 5-HT3-recep-tors compared with other receptor types is greater than 1000. In animals and in man, ondansetron has no overt actions on cardiovascular parameters and there are no effects on normal behaviour [7]. 

Pharmacology Apraclonidine hydrochloride is a relatively selective -adrenergic agonist. When instilled into the eyes, apraclonidine reduces intraocular pressure (lOP) and has minimal effect on cardiovascular parameters. 

Renal/Hepatic function impairment Although the topical use of apraclonidine has not been studied in renal failure patients, structurally related clonidine undergoes a significant increase in half-life in patients with severe renal impairment. Close monitoring of cardiovascular parameters in patients with impaired renal function is advised if they are candidates for topical apraclonidine therapy. Close monitoring of cardiovascular parameters in patients with impaired liver function is also advised as... 

Inappropriate use of oxytocin can lead to uterine rupture, anaphylactoid and other allergic reactions, and possibly maternal death. Prolonged stimulation of uterine contractions can result in the following fetal adverse reactions persistent uteroplacental insufficiency, sinus bradycardia, premature ventricular contractions, other arrhythmias, and fetal death. Prolonged use of oxytocin can lead to water intoxication secondary to the antidiuretic hormone-like effects of oxytocin. Maternal and fetal cardiovascular parameters should be monitored during oxytocin administration. 

TABLE 23.4 Suggested Guidelines for Cardiovascular Parameters in Children and Adolescents Treated with Tricyclics... 

Barrett-Connor E. Efficacy and safety of estrogen/androgen therapy. Menopausal symptoms, bone, and cardiovascular parameters. J Reprod Med 1998 43(Suppl 8) 746-52. 

Cardiovascular effects have been evaluated in acute, intermediate, and chronic oral studies with experimental animals. Acute studies have been limited to histological examination of the heart following 1-day or 10-day gavage exposure of rats to doses as high as 198 mg barium/kg/day as barium chloride (Borzelleca et al. 1988). No microscopic lesions of the heart were observed. Other cardiovascular parameters were not evaluated. 

Cardiovascular parameters such as arterial blood pressure and heart rate can be measured in conscious, free-moving rats using commercially available radio telemetry systems (Deveney et al. 1998). Such systems... 

Instrumented animals may be reused after appropriate washout periods on the assumption that the compounds in the doses tested cause no reversible damage. Since the cardiovascular parameters measured are sensitive to the overall well being of the animals, changes in baseline conditions should be examined for detecting possible compound-related toxicities. Assuming such toxicities are not observed, animals can be maintained for over one year with appropriate care. 

The hemodynamic effects of compounds supposed to affect the cardiovascular system are evaluated by measuring preload and afterload of the heart, contractility, heart rate, cardiac output and peripheral or coronary flow. To measure these cardiovascular parameters accurately, the use of larger animals such as dogs or pigs is necessary. This experimental model allows the classification of test drugs according to their action as having ... 

To assess the safety margin of an inhalation anesthetic, not only should the ED50 values but also the maximally effective dose and the dose with a minimal danger of fatal outcome be determined. In particular, cardiovascular parameters are observed (Kissin et al. 1983). 

Capeless EL, Clapp JF. When do cardiovascular parameters return to their preconception values Am J Obstet Gynecol 1991 165 883-6. 

Direct measurement of blood pressure requires insertion of a cannula into an artery and generally a vein, respectively, to allow blood pressure and heart rate to be monitored, and also the administration of drugs. The animal is allowed to recover from anaesthesia, and the cardiovascular parameters are monitored in the conscious animal via the arterial cannula. 

These experiments are performed in conscious animals, and no effect on other parameters such as blood pressure and heart rate can be monitored unless the animals are anaesthetized. However, the use of anaesthetics can reduce the blood pressure and inhibit neurogenic reflexes, thus masking any changes in cardiovascular parameters. Nevertheless, by careful comparison with standard drugs, relative falls in blood pressure can be assessed between compounds. 

Both alfentanil and propofol were effective and safe, provided respiratory and cardiovascular parameters were routinely monitored. 

In a comparison of the dysrhythmogenic potential of a series of second-generation antihistamines, the antihistamines were given intravenously and electrocardiographic and cardiovascular parameters (blood pressure and heart rate) were measured. The lowest dose that produced significant prolongation of the QT , interval... 

McCullough LS, Stone WA, Delaunois AL, Reier CE, Hamelberg W. The effect of dimethyl tubocurarine iodide on cardiovascular parameters, postganglionic sympathetic activity, and histamine release. Anesth Analg 1972 51(4) 554-9. 

In the non-exercising horse, increased blood lactate concentrations are sufficient evidence of a metabolic disturbance to initiate fluid therapy. They are an indication of poor tissue perfusion or increased circulating epinephrine (adrenaline) concentrations (James et al 1999). Hypovolemia and endotoxemia are common causes of increased lactate concentrations in the horse. Endotoxemia increases tissue lactate production both through circulatory changes, which reduce blood flow to the tissues and inappropriate anaerobic metabolism (Fink 1997). Whereas lactate is a good indicator of the need to start fluid therapy, continued high lactate concentrations should be assessed in the context of cardiovascular parameters, such as pulse rate, urine output and blood pressure, because decreases in plasma lactate concentration... 

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