Sevoflurane modulation of Ca2+ regulation in skeletal muscle sarcoplasmic reticulum vesicles from young and mature rabbits

Introduction: Developmental differences in splice variants of the two key sarcoplasmic reticulum (SR) calcium regulatory proteins, ryanodine (RyR1), and sarcoendoplasmic reticulum calcium pump (SERCA1) have been linked to various neuromuscular disorders, but not malignant hyperthermia (MH). However, it is unclear whether an age‐related difference in volatile anesthetic‐mediated SR calcium function exists that could add to our current understanding of the clinical presentation of MH syndrome and provide insight into molecular mechanisms for general anesthesia that may have other physiologic and/or pathophysiologic significance. Therefore, the effects of sevoflurane on intracellular calcium regulation in isolated SR membrane vesicles from the skeletal muscle of healthy young rabbits were compared to their adult counterpart using an established in vitro model with the assumption that exposure to sevoflurane would elicit a weaker response in the young SR. Methods: Through dual wavelength spectroscopy of Ca²⁺: Arsenazo III difference absorbance, the effects of sevoflurane on SR Ca²⁺ uptake rate and release in heavy and light fraction SR membrane vesicles isolated from the white muscle of anesthetized, postweaned (age = 6 weeks, n = 5) and adult (age = 6 months, n = 5) male New Zealand rabbits were examined. Results: The adult group showed a 50% increase in Ca²⁺ uptake rate from control at both subclinical and clinically relevant anesthetic concentrations, whereas in the SR from the younger animals, Ca²⁺ uptake rate was not altered by any concentration of sevoflurane. The sensitivity of both the low and high affinity Ca²⁺‐binding sites on RyR1 was increased by sevoflurane to the same extent in the SR vesicles from the young and mature adult rabbits. Interestingly, a greater potency of sevoflurane for the high affinity‐binding site was identified, and this was independent of age. Conclusions: These findings suggest that the sensitivity of the SR to sevoflurane‐mediated Ca²⁺ uptake may be increased with maturity, while an analogous developmental effect on RyR1 is less probable. Nonetheless, this study shows for the first time that a potent inhalational agent such as sevoflurane can influence the high affinity SR calcium‐binding site by lowering the extraluminal concentration of calcium necessary to trigger calcium release. While this may not be of consequence when inhaled anesthetics are administered to normal children or adults, it may have life‐threatening consequences in carriers of RyR1 mutations.     

Termination of Tachycardias by Transesophageal Electrical Pacing

To evaluate the therapeutic significance of noninvasive transesophageal pacing for termination of tachycardias the method of rapid atrial or ventricular transesophageal pacing was used in 233 patients with different tachycardiac arrhythmias. We were able to terminate atrial flutter in 136 of 162 patients by transesophageal rapid atrial stimulation (conversion to sinus rhythm in 75 cases, induction of atrial fibrillation in 61 cases). Atrial tachycardias were interrupted in 17 of 23 patients (sinus rhythm in 11 cases, atrial fibrillation in six cases). AV reciprocating/AV nodal supravenrricular reentry tachycardias were terminated in 62 of 63 patients (sinus rhythm in 58 cases, atrial fibrillation in four cases). By transesophageal rapid ventricular pacing ventricular tachycardias could be terminated in ten of 15 patients. The success rate of transesophageal pacing was influenced by the pacing rate, by the type of tachycardiac arrhythmia inclusive by the type of atrial flutter and by the tachycardia's cycle length. Because the success rates are comparable with invasive technique and the procedure is simpler, the noninvasive transesophageal antitachycardiac pacing should be respected as the method of the first choice in patients with supraven-tricular tachycardias.     

On the mechanism of glucose release from the muscle of juvenile diabetics in acute insulin deficiency

In fifty-three healthy subjects and twenty-three juvenile diabetics the measurement of arterial and deep venous glucose concentrations showed that the substrate was taken up by the tissues of the forearm of all the healthy subjects and released from it in all the diabetic ones. In six of the diabetics glucose output was accelerated almost five-fold during the intrabrachial arterial administration of metaproterenol (1.62 nmol/min), indicating that basal glucose release from muscle may result from enhanced glycogenolysis during acute insulin deficiency. In line with this view a reduction of glucose uptake by muscle was observed in six healthy subjects receiving metaproterenol infusion. However, since the production of lactate by the forearm appeared to be smaller in the diabetics, the basal glucose output could also partly be due to impaired glycolysis. These data suggest that the glucose released from muscle during acute insulin deficiency may be of clinical importance, especially when the rate of glycogenolysis is further stimulated by, for example, enhanced catecholamine drive.     

Rate Response of a Closed-Loop Stimulation Pacing System to Changing Preload and Afterload Conditions

Closed-loop stimulation (CLS) is a new sensor concept for rate adaptive pacing measuring changes in the unipolar right ventricular impedance, which correlates to changes of the right ventricular contractility and reflects the autonomic nervous innervation of the heart. Some patients do not tolerate the CLS mode because of inappropriate tachycardia, mainly related to postural changes. This study tested if the rate response of the CLS sensor is influenced not only by myocardial contractility but also by rapid changes in right ventricular filling. In 12 patients (10 men, median age 77 years) with a Biotronik Inos²-CLS DDDR pacemaker and 14 controls (13 men, median age 59 years) head-up tilt and handgrip testing was performed to provoke rapid changes in pre- and afterload. Tilting the pacemaker patients resulted in a nonphysiological steep increase of the sensor rate (increase >20 beats/min, peak after 1 minute, return to baseline within 2–3 minutes), which was significantly different from the control group, showing only a slight rise in intrinsic heart rate immediately after tilting. Simultaneously to the rapid increase in sensor rate, the pacemaker patients showed a marked orthostatic decline of systolic blood pressure. During handgripping, heart rate and blood pressure curves were similar in both groups. In patients with this CLS pacemaker, rapid preload reduction during head-up tilting caused an overshooting sensor rate increase, reproducing the authors' clinical observation of postural pacemaker tachycardia in some patients. Consequently, they concluded that the rate response of the CLS pacing system can be inappropriately influenced by rapid shifts of blood volume, affecting right ventricular filling. (PACE 2003; 26[Pt. I]:1504–1510)