Jose M. Brum

Vasodilation and mechanism of action of propofol in porcine coronary artery.

BackgroundA decrease in myocardial perfusion pressure may reduce myocardial blood flow. However, it may not significantly affect myocardial perfusion when in presence of a concurrent coronary artery vasodilation. However, the effects of propofol in coronary arteries are not well determined. In this study, the effects of propofol on porcine coronary artery responses to vasoactive agents that operate through voltage- and receptor-mediated calcium mechanisms were investigated. MethodsHearts of adult pigs (n = 103) were obtained from a slaughter house, and the left anterior descending coronary arteries were dissected. The arteries were cut into vessel rings and prepared with and without the endothelium organ chambers filled with buffered salt solution. The effect of propofol (10–7, 10–6, 10–5, and 10–4M) on vascular smooth muscle contraction caused by intracellular Ca2+-influx through voltage- and receptor-mediated mechanism also was studied at a cellular level. ResultsPropofol relaxed coronary rings that were contracted by KCI, norepinephrine (NE), serotonin (5-HT), or carbachol (CCh). The minimal concentrations of propofol that produced significant vasorelaxation ranged from 3.16 X 10–7 M to 3.16 X 10–6 M. Vasodilation was more pronounced in rings contracted by NE, 5-HT, and CCh than by KCI. Propofol (10–5 M) attenuated coronary vasoconstriction in response to cumulative concentrations of KCI, NE, 5-HT, and acetylcholine. Maximal contractions produced by NE and 5-HT were inhibited to a greater degree than contractions produced by KCI. Propofol at concentrations of 10–5 M and higher attenuated a contraction in response to CaCl2 in vascular rings depolarized by KCI, but concentrations of 10–5 M did not attenuate contractions. Vasoconstriction in response to calcium entry in the presence of NE (and nifedipine 10–6 M) was attenuated by propofol at concentrations of 10–6 M and higher. Caffeine-induced contraction, caused by intracellular calcium release, was attenuated only at 10–4 M of propofol. ConclusionsPropofol possesses vasodilator effect and attenuates the effects of vasoconstrictor agents in porcine coronary artery. Further, an antagonism of calcium channels may be responsible for these effects of propofol.

Heart rate, heart rate variability, and blood pressure during perioperative stressor events in abdominal surgery

STUDY OBJECTIVE To define the behavior of power spectral heart rate variability (PSHR) during potentially stressful events in the perioperative period, and relate it to changes in blood pressure (BP) and heart rate (HR). DESIGN Longitudinal clinical study. SETTING Operating room and recovery suites of a large tertiary care referral center. PATIENTS 26 ASA physical status I, II, and III patients undergoing elective abdominal surgery. INTERVENTIONS Anesthesia was induced with thiopental sodium and fentanyl, and maintained with isoflurane/nitrous oxide (N2O)/relaxant or enflurane/N2O/relaxant. The trachea was intubated and intraabdominal surgery was performed. MEASUREMENTS AND MAIN RESULTS Observations consisted of HR, noninvasive blood pressure, and PSHR. They were made before and after induction of anesthesia, tracheal intubation, and surgical incision, and during maximal surgical stimulation and skin closure. HR and mean arterial pressure (MAP) maxima were also recorded for one hour before and after emergence from anesthesia. PSHR was obtained using a special algorithm and data acquisition system for real time spectral analysis of the instantaneous HRversus time function. The HR power spectrum parameters analyzed were low-frequency (LFA; powerband = 0.04 to 0.10 Hz), respiratory-induced frequency (RFA; powerband = respiratory frequency +/- 0.06 Hz), and the ratio of LFA to RFA. With induction of anesthesia, only RFA power decreased significantly. LFA power reduction became significant only after intubation and continued so until after incision. Immediately after induction, the decline in RFA power (vs. preinduction) was more pronounced when compared with the decline in LFA power (76% vs. 34%; p = 0.01). Hence, the ratio LFA/RFA increased significantly after induction of anesthesia. It was significantly higher than at postintubation, preincision, or skin closure. A significant elevation in LFA, LFA/RFA ratio, and BP occurred with maximal abdominal surgical stimulation. Only preinduction LFA, RFA, and LFA/ RFA ratio were predictive of MAP changes with induction of anesthesia (p = 0.006). In 8 of the 15 patients who had MAP changes of at least 10 mmHg with induction, PSHR indices correctly predicted a change of this magnitude. Late intraoperative HR maxima were positively correlated with the change in HR and incision (r2 = 0.58; p < 0.01). The change in BP with incision was positively correlated with early postoperative HR maxima (r2 = 0.60; p < 0.01). CONCLUSIONS On anesthetic induction, preoperative, but not intraoperative, spectral indices were predictive of BP changes. Power spectral analysis of HR may provide information about the autonomic state that is not evident from BP or HR. The HR power spectrum, in particular, indicated a striking autonomic imbalance immediately after the induction of anesthesia despite stable HR and BP. LFA and LFA/RFA ratio appeared to track sympathetic autonomic activation during abdominal surgical stimulation, but not during other perioperative stressor events.

Analysis of heart rate variability to assess hemodynamic alterations following induction of anesthesia

Extensive changes in hemodynamics and cardiac rhythm during induction of anesthesia may be mediated by altered responses of the autonomic nervous system to anesthetic agents. Analysis of the power spectrum of the heart rate (PSHR) variability can supply information about the autonomic nervous system, and may be used in order to assess this phenomenon. In this study, 78 patients undergoing coronary artery bypass graft surgery were evaluated. Anesthesia was induced with sufentanil, and neuromuscular blockade with vecuronium, a combination that may cause a decrease in heart rate. Before and after induction of anesthesia, the heart rate (HR), blood pressure (BP), cardiac output (CO), cardiac index (CI), and PSHR components were recorded. PSHR was obtained by using a special algorithm and data acquisition system for real-time spectral analysis. A low-frequency component (LFa, mainly sympathetic) was analyzed from a band of 0.04 Hz to 0.1 Hz. A high-frequency component (RFa, parasympathetic) was identified by the respiratory frequency spectrum. Alterations of the heart rate after induction of anesthesia were defined in order to separate the patient population into two groups: slow heart rate (slow-HR) and stable heart rate (stable-HR). Slow heart rate was defined as a decrease in HR of more than 20% of the baseline value. The variables were analyzed and compared between the slow-HR (n = 25) and stable-HR (n = 53) groups in order to verify the possibility of identifying patients prone to hemodynamic changes after anesthesia induction. There were no differences in preoperative HR, BP, CO, or CI between groups before anesthesia induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Attenuated vascular reactivity in dogs with anteroventral third ventricle lesions.

Lesion of the anteroventral portion of the third cerebral ventricle causes hypernatremia, adipsia, and attenuation of the pressor response to intravenous administration of angiotensin II and norepinephrine. In addition, these lesions prevent the development of several experimental models of hypertension. In this study, a lesion of the third cerebral ventricle region was made in 14 dogs. In seven dogs in which hypernatremia developed the lesions included the organum vasculosum of the lamina tenninalis; seven animals in which the circumventricnlar organ was spared by the lesion remained normonatremic Vascular responsiveness of isolated right carotid artery rings to angiotensin II and phenylephrine was assessed 3 days after lesioning the anteroventral portion of the third cerebral ventricle. In endothelium-denuded ring vessels, vasoconstrictor responses to phenylephrine were significantly decreased in animals both with and without inclusion of the organum vasculosum of the lamina tenninalis. A similar effect was observed in intact vessels of dogs in which the circumventricular organ was spared but not in those with lesions that included this area. In contrast, angiotensin Il-induced vasoconstriction was significantly decreased in the arteries with intact endothelium of both groups of lesioned animals. These data show that lesion of the anteroventral third ventricle area alters α-adrenergic and angiotensin II vascular responsiveness in isolated carotid artery rings with the possible participation of the endothelium.

Effects of opioids on vasoresponsiveness of porcine coronary artery

Myocardial ischemia during surgery can be caused by coronary vasospasm. Neurohumoral mechanisms are involved in this phenomenon, and various substances have been suggested as possible causes, including acetylcholine, histamine, and norepinephrine. The responses of isolated porcine coronary arteries (from 117 pig hearts) with (E+) and without (E-) endothelium to these agents were investigated in the presence of fentanyl, sufentanil, and morphine. Fentanyl significantly shifted to the right, in a concentration-dependent fashion, the concentration-response curve to acetylcholine. This effect was not different between E+ and E- rings. Neither sufentanil nor morphine altered acetylcholine-induced contraction of porcine coronary arteries. Naloxone did not antagonize the suppressive effect of fentanyl on acetylcholine-induced contraction. The response of porcine coronary arteries to norepinephrine was decreased only at very high concentrations of fentanyl. Neither sufentanil nor morphine altered norepinephrine-induced contraction of porcine coronary arteries. Fentanyl, sufentanil, and morphine had no effect on histamine-induced contraction. We conclude that tentanyl antagonized acetylcholine-induced contraction of porcine coronary arteries. This effect of fentanyl seems to be caused by a direct effect on smooth muscle cells and is not opioid-receptor mediated.

Role of Nitric Oxide in Systemic Hemodynamic Responses to Dobutamine, Epinephrine, and Amrinone

OBJECTIVE This study was designed to investigate the extent to which the systemic vasodilator effects of dobutamine, epinephrine, and amrinone are modulated by the endothelium-derived relaxing factor, nitric oxide (NO). DESIGN This was a prospective study of low and high doses of the agonists before and after inhibition of NO synthesis. SETTING Experiments were performed in the basic research laboratories of the Center for Anesthesiology Research. PARTICIPANTS Pentobarbital-anesthetized, intact Sprague-Dawley rats were studied in seven separate groups of eight rats each. INTERVENTIONS The systemic vasodilator responses to the agonists were assessed before and after the administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester. MEASUREMENTS AND MAIN RESULTS Decreases in systemic vascular resistance in response to dobutamine and epinephrine were not observed after inhibition of NO synthesis, whereas the decrease in systemic vascular resistance in response to amrinone was still apparent. CONCLUSIONS The results suggest that dobutamine and epinephrine produce systemic vasodilation through the release of NO, whereas amrinone produces vasodilation independent of NO release.

Effect of cocaine on the contracture response to 1% halothane in patients undergoing diagnostic muscle biopsy for malignant hyperthermia

Two case reports have cited the recreational use of cocaine as possible trigger of a malignant hyperthermia (MH) crisis. We evaluated whether toxic concentrations of cocaine altered the in vitro muscle response to halothane during contracture tests for MH. Twenty-two patients were studied. Muscle biopsies were obtained and first tested for MH susceptibility with 3% halothane and caffeine contracture testing. Ten patients were diagnosed as MH-susceptible and 12 as MH non-susceptible, in accordance with the North American Malignant Hyperthermia Group protocol. Then, muscle strips were exposed to 1% halothane in the presence and absence of 0.1 mmol · L−1 cocaine. Cocaine alone did not affect baseline muscle tension in either group. With 1% halothane, MH non-susceptible muscle showed no contracture with or without cocaine. In contrast, in the presence of 1% halothane, MH-susceptible muscle showed either no change in contracture (six patients), an increase (two patients), or a decrease (two patients) when exposed to cocaine. However, the overall effect of cocaine on muscle contracture in the presence of 1% halothane was insignificant in both groups. We conclude that cocaine, even at toxic levels, does not have a direct effect on skeletal muscle contractility and thus is safe for MH-susceptible patients.RésuméDeux observations ont déjà mentionné l’usage illégal de la cocaïne comme cause déclenchante de crises d’hyperthermie maligne (HM). Nous recherchons si des concentrations toxiques de cocaïne pourraient changer in vitro la réponse des tests de contracture musculaire à l’halothane 1% spécifiques pour l’HM. L’étude porte sur vingt-deux patients. Des biopsies musculaires sont d’abord prélevées et soumises à l’épreuve de contracture à l’halothane 3% et à celle de la caféine. Chez dix patients on diagnostique une susceptibilité à l’HM en conformité avec le protocole nord-américain du groupe d’HM alors que 12 patients sont déclarés normaux. Les lambeaux musculaires sont ensuite exposé à l’halothane 1% en présence ou non de cocaïne 0,1 mmol · L−1. L’exposition à la cocaine seule ne change pas la tension musculaire initiale dans les deux groupes. Avec halothane 1%, le muscle non susceptible à l’HM ne présente pas de contracture que ce soit avec ou sans cocaïne. Par contre, avec l’halothane 1%, le muscle susceptible à l’HM en présence de cocaïne montre aucun changement (six patients), une augmentation (deux patients) ou une diminution de la contracture (deux patients). Cependant, en général, l’effet de la cocaïne sur la contracture musculaire en présence de cocaïne 1% est négligeable pour les deux groupes. Nous concluons que la cocaïne, même à concentrations toxiques, n’a pas d’effets directs sur la contractilité du muscle squelettique et ainsi ne présente pas de danger pour les patients susceptibles à l’HM.