Biomedical subjects

D C Sigg

Publications and source records attributed to D C Sigg.

6 recordsLinked to original sources

PubMed2005

The antiarrhythmic effect of n-3 polyunsaturated fatty acids: modulation of cardiac ion channels as a potential mechanism.

Sudden cardiac death remains one of the most serious medical challenges in Western countries. Increasing evidence in recent years has demonstrated that the n-3 polyunsaturated fatty acids (PUFAs) can prevent fatal ventricular arrhythmias in experimental animals and probably in humans. Dietary supplement of fish oils or intravenous infusion of the n-3 PUFAs prevents ventricular fibrillation caused by ischemia/reperfusion. Similar antiarrhythmic effects of these fatty acids are also observed in cultured mammalian cardiomyocytes. Based on clinical observations and experimental studies in vitro and in vivo, several mechanisms have been postulated for the antiarrhythmic effect of the n-3 PUFAs. The data from our laboratory and others have shown that the n-3 PUFAs are able to affect the activities of cardiac ion channels. The modulation of channel activities, especially voltage-gated Na(+) and L-type Ca(2+) channels, by the n-3 fatty acids may explain, at least partially, the antiarrhythmic action. It is not clear, however, whether one or more than one mechanism involves the beneficial effect of the n-3 PUFAs on the heart. This article summarizes our recent studies on the specific effects of the n-3 PUFAs on cardiac ion channels. In addition, the effect of the n-3 PUFAs on the human hyperpolarization-activated cyclic-nucleotide-modulated channel is presented.

Animals↗

PubMed2001

Opioid preconditioning: myocardial function and energy metabolism.

BACKGROUND: Opioid receptor agonists are involved in ischemic preconditioning and natural hibernation. The aim of this study was to determine whether pretreatment with D-Ala2-Leu5-enkephalin or morphine confers cardioprotection in large mammalian hearts. We assessed myocardial functional recovery and global energy metabolism after ischemic cold storage. METHODS: After pretreatment with D-Ala2-Leu5-enkephalin, morphine sulfate, or saline (n = 6 each), swine hearts were excised and stored for 75 minutes at 4 degrees C, then reperfused in a four-chamber isolated working heart apparatus. Serial myocardial biopsies were performed to assess cellular energy metabolism. RESULTS: Improved systolic (cardiac output, contractility) and diastolic (tau) left ventricular functions were observed in hearts pretreated with D-Ala2-Leu5-enkephalin or morphine. These benefits were not correlated with changes in high-energy phosphate levels. Cardiac enzyme leakage (creatine kinase, troponin-I) was similar among treated and control groups. Lactate efflux increased significantly in controls, but not in opioid-pretreated hearts (p < 0.01) at 75 minutes of reperfusion. CONCLUSIONS: D-Ala2-Leu5-enkephalin and morphine pretreatments improve postischemic function after cold storage of swine hearts. Postischemic lactate reduction, but not high-energy phosphate levels, may account for the observed cardioprotective effects.

Animals↗

PubMed2001

Shiver suppression using focal hand warming in unanesthetized normal subjects.

BACKGROUND: A decrease of 1 or 2 degrees C in core temperature may provide protection against cerebral ischemia. However, during corporeal cooling of unanesthetized patients, the initiation of involuntary motor activity (shiver) prevents the reduction of core temperature. The authors' laboratory previously showed that focal facial warming suppressed whole-body shiver. The aim of the current study was to determine whether the use of hand warming alone could suppress shiver in unanesthetized subjects and hence potentiate core cooling. METHODS: Subjects (n = 8; healthy men) were positioned supine on a circulating water mattress (8-15 degrees C) with a convective-air coverlet (14 degrees C) extending from their necks to their feet. A dynamic protocol was used in which focal hand warming was used to suppress involuntary motor activity, enabling noninvasive cooling to decrease core temperatures. The following parameters were monitored: (1) heart rate; (2) blood pressure; (3) core temperature (rectal, tympanic); (4) cutaneous temperature and heat flux; (5) subjective shiver level (SSL scale 0-10) and thermal comfort index (scale 0-10); (6) metabolic data (n = 6); and (7) electromyograms. RESULTS: During cooling without hand warming, involuntary motor activity increased until it was widespread. After subjects reported whole-body shiver (SSL > or = 7), applied hand warming, in all cases, reduced shiver levels (SSL < o r= 3), decreased electromyographic root mean square amplitudes, and allowed core temperature to decrease from 37.0 +/- 0.2 to 35.9 +/- 0.5 degrees C (measured rectally). CONCLUSIONS: Focal hand warming seems to be valuable in minimizing or eliminating the need to suppress involuntary motor activity pharmacologically when it is desired to induce or maintain mild hypothermia; it may be used in conjunction with facial warming or in cases in which facial warming is contraindicated.

Adult↗

PubMed2000

Malignant hyperthermia phenotype: hypotension induced by succinylcholine in susceptible swine.

BACKGROUND: Succinylcholine causes immediate and severe arterial hypotension in swine with the malignant hyperthermia phenotype. The underlying mechanisms are unknown. METHODS: Malignant hyperthermia-susceptible (MHS; n = 10) and normal swine (n = 5) were anesthetized with thiopental. The following were monitored: electrocardiogram; arterial blood pressure; pulmonary artery, central venous, and left and right ventricular pressure; cardiac output; end-tidal carbon dioxide; core temperature; peripheral-blood flows; and arterial blood gases. After a control period, 2 mg/kg succinylcholine was given intravenously. Three MHS animals received 1 mg/kg vecuronium and two MHS animals received 2.5 mg/kg dantrolene intravenously. The effects of succinylcholine on left and right ventricular pressure and contractility were analyzed in isolated hearts. The effects of 0.06 mm succinylcholine on isometric tension development were recorded in isolated femoral artery rings. RESULTS: Succinylcholine caused an early, severe decrease in blood pressure, cardiac output, left ventricular pressure, and left ventricular contractility in MHS swine but not in normal swine; no significant differences were found in heart rate, right ventricular parameters, systemic vascular resistance, and preload (pulmonary diastolic pressure, central venous pressure). The succinylcholine-induced hypotension and associated effects were not prevented by dantrolene. However, pretreatment with high-dose vecuronium prevented not only the cardiovascular depression, but also MH. In addition, no phenotypic differences of succinylcholine on contractility or left ventricular pressure were observed in the isolated working hearts. Similary, succinylcholine did not cause a significantly different relaxation in rings in either phenotype. CONCLUSION: Succinylcholine-induced hypotension occurred before muscle hypermetabolism in MHS swine. Succinylcholine had no differential physiologic effects on either the isolated heart or on isolated arteries. This hypotension could not be prevented by dantrolene but was prevented by pretreatment with high-dose vecuronium. Thus, an indirect mechanism such as the release of a cardiac depressant from skeletal muscle may have caused this hypotensive response.

Animals↗

PubMed1999

The potential for increased risk of infection due to the reuse of convective air-warming/cooling coverlets.

BACKGROUND: The use of convective air warming and/or cooling for the prevention of hypothermia or to induce hypothermia is growing rapidly. To date, there is no information available as to the potential risks for infection associated with either the post-surgical reuse or the repositioning of coverlets closer to the wound. We hypothesized that use of coverlets either intra- or postoperatively leads to increased contamination. METHODS: The bacterial contamination of commercially available coverlets before (control group, n = 10) and after patient application (n = 18) was investigated. From 3 predetermined sites, 1 cm x 2 cm pieces of coverlet were removed and analyzed for bacterial contamination. RESULTS: Even prior to use, coverlet samplings provided identifiable contamination (3 out of 30 sites, 10%), but this could be within our study's sampling error. Nevertheless, following clinical use the frequency of contamination was considerably increased; 17 out of 57 sampled sites (31.5%) elicited contamination (P < 0.05, Fisher's exact test). CONCLUSION: This study demonstrates that the use of the coverlets, intra- or postoperatively, can lead to significant bacterial contamination. It is concluded that it is not advisable to reuse coverlets for multiple clinical applications.

Bedding and Linens↗

PubMed1999

Facial warming increases the threshold for shivering.

A decrease of 1-2 degrees C core temperature provides protection against cerebral ischemia. However, shivering usually prevents reduction in core temperature in unanesthetized patients. Therefore, it was tested whether facial and airway heating increases the shivering threshold and enables core cooling in unanesthetized patients. Nine trials were performed on seven healthy male volunteers. Each subject was positioned supine on a circulating-water mattress (8-15 degrees C) with a convective-air coverlet (15-18 degrees C) extending from the neck to the feet. A dynamic study protocol governed by individualized physiological responses was used. Focal facial (and airway) warming was employed to suppress involuntary motor activity (muscle tensing, shivering) and, thereby, enabling noninvasive cooling to lower the core temperature. The following parameters were monitored: 1) heart rate, 2) blood pressure, 3) core temperature (tympanic, axilla, and rectal), 4) cutaneous temperatures, and 5) a subjective shiver index (scale 1-10). In three, electromyograms and infrared thermographs were also obtained. Upon cooling without facial and airway warming, involuntary motor activity increased until it was widespread. This vigorous motor activity prevented any significant lowering of core temperature or caused it to slightly increase. Subsequently, in all subjects, within seconds after the application of facial focal warming, motor activity was suppressed almost completely, and within minutes core temperatures significantly decreased. Preliminary studies described here indicate that focal facial warming applied during active whole body cooling to initiate mild hypothermia might minimize the need to pharmacologically suppress involuntary motor activity. Such a procedure might be useful for initiating as soon as possible (such as during emergency transport), cerebral mild hypothermia in order to maximize protection and thus improve outcome in neurologically injured patients (head trauma, stroke).

Adult↗