To identify genetic factors influencing cardiac conduction, we carried out a genome-wide association study of electrocardiographic time intervals in 6,543 Indian Asians. We identified association of a nonsynonymous SNP, rs6795970, in SCN10A (P = 2.8 x 10(-15)) with PR interval, a marker of cardiac atrioventricular conduction. Replication testing among 6,243 Indian Asians and 5,370 Europeans confirmed that rs6795970 (G>A) is associated with prolonged cardiac conduction (longer P-wave duration, PR interval and QRS duration, P = 10(-5) to 10(-20)). SCN10A encodes Na(V)1.8, a sodium channel. We show that SCN10A is expressed in mouse and human heart tissue and that PR interval is shorter in Scn10a(-/-) mice than in wild-type mice. We also find that rs6795970 is associated with a higher risk of heart block (P < 0.05) and a lower risk of ventricular fibrillation (P = 0.01). Our findings provide new insight into the pathogenesis of cardiac conduction, heart block and ventricular fibrillation.

Prolonged mechanical unloading (UN) of the heart is associated with detrimental changes to the structure and function of cardiomyocytes. The mechanisms underlying these changes are unknown. In this study, we report the influence of UN on excitationcontraction coupling, Ca 2؉ -induced Ca 2؉ release (CICR) in particular, and transverse (t)-tubule structure. UN was induced in male Lewis rat hearts by heterotopic abdominal heart transplantation. Left ventricular cardiomyocytes were isolated from the transplanted hearts after 4 wk and studied using whole-cell patch clamping, confocal microscopy, and scanning ion conductance microscopy (SICM). Recipient hearts were used as control (C). UN reduced the volume of cardiomyocytes by 56.5% compared with C (UN, n‫;09؍‬ C, n‫;95؍‬ P<0.001). The variance of time-to-peak of the Ca 2؉ transients was significantly increased in unloaded cardiomyocytes (UN 227.4؎24.9 ms 2 , n‫24؍‬ vs.

Aims Ca2+‐induced Ca2+ release (CICR) is critical for contraction in cardiomyocytes. The transverse (t)‐tubule system guarantees the proximity of the triggers for Ca2+ release [L‐type Ca2+ channel, dihydropyridine receptors (DHPRs)] and the sarcoplasmic reticulum Ca2+ release channels [ryanodine receptors (RyRs)]. Transverse tubule disruption occurs early in heart failure (HF). Clinical studies of left ventricular assist devices in HF indicate that mechanical unloading induces reverse remodelling. We hypothesize that unloading of failing hearts normalizes t‐tubule structure and improves CICR. Methods and results Heart failure was induced in Lewis rats by left coronary artery ligation for 12 weeks; sham‐operated animals were used as controls. Failing hearts were mechanically unloaded for 4 weeks by heterotopic abdominal heart transplantation (HF‐UN). HF reduced the t‐tubule density measured by di‐8‐ANEPPS staining in isolated left ventricular myocytes, and this was reversed by unloading. The deterioration in the regularity of the t‐tubule system in HF was also reversed in HF‐UN. Scanning ion conductance microscopy showed the reappearance of normal surface striations in HF‐UN. Electron microscopy revealed recovery of normal t‐tubule microarchitecture in HF‐UN. L‐type Ca2+ current density, measured using whole‐cell patch clamping, was reduced in HF but unaffected by unloading. The variance of the time‐to‐peak of the Ca2+ transient, an index of CICR dyssynchrony, was increased in HF and normalized by unloading. The increased Ca2+ spark frequency observed in HF was reduced in HF‐UN. These results could be explained by the recoupling of orphaned RyRs in HF, as indicated by immunofluorescence. Conclusions Our data show that mechanical unloading of the failing heart reverses the pathological remodelling of the t‐tubule system and improves CICR.

We have examined the effects of isoflurane (0.6-2.9% end-tidal) on the auditory evoked response (AER) in six patients before elective surgery. Isoflurane produced significant dose-related changes in the AER: reductions in amplitude and increases in latency of the cortical waves Pa and Nb, and increases in the latency of the brainstem waves III and V. When isoflurane was compared with halothane and enflurane using an MAC-based comparison, we found no differences in the effect of the three agents on the amplitude of the early cortical waves, although the latencies showed significant differences. The consistent dose-related effect on the amplitudes of the cortical waves implies that the AER could be a promising index of the depth of anaesthesia.

Objective Octogenarians, as the fastest growing stratum of the population and with the highest prevalence of coronary artery disease, are being increasingly referred for coronary artery bypass grafting (CABG). The general perception is that the presence of comorbidities and the propensity for neurological injury expose them to a higher risk for mortality and morbidity after conventional on-pump CABG, and therefore, off-pump CABG should be preferentially offered to octogenarians to improve outcomes. This study evaluates the in-hospital outcomes and predictors of mortality and stroke in octogenarians undergoing on- and off-pump CABG at our institution. Methods From January 2000 to December 2010, a total of 290 octogenarians underwent off-pump (n = 217) and on-pump (n = 73) CABG. Their data were prospectively entered into the cardiac surgery database (Patients Analysis & Tracking System; Dendrite Clinical Systems, Ltd, Oxford, England, United Kingdom) and analyzed retrospectively. Outcome measures included in-hospital mortality, major complications, and length of stay. Multivariate analysis was performed to identify predictors of combined outcome of in-hospital mortality and stroke. Results The mean ± SD age of the patients was 82 ± 2.0 years. Preoperative demographics were similar for the on-pump and off-pump groups. The patients who underwent off-pump CABG had a lower number of distal anastomoses performed compared with the patients who underwent on-pump CABG [mean difference, 0.2; 95% confidence interval (CI), 0.02–0.4; P = 0.03]. However, the ratio of grafts (received/needed) was the same in both groups. In-hospital mortality for the entire cohort was 7.2%, with no significant difference between the groups for death (6.0% vs 11.0%; P = 0.08), stroke (2.8% vs 2.8%; P = 1.0), other major complications, and length of hospital stay. Independent predictors of combined outcome identified from the multiple logistic model included heart failure [odds ratio (OR), 4.4; 95% CI, 1.5–13.0; P = 0.008], diabetes (OR, 2.6; 95% CI, 1.0–6.0; P = 0.046), nitrate infusion (OR, 2.9; 95% CI, 1.1–8.0; P = 0.04), postoperative renal failure requiring hemofiltration (OR, 8.6; 95% CI, 3.5–21.1; P < 0.001), and postoperative ventricular arrhythmias (OR, 7.3; 95% CI, 1.9–27.8; P = 0.009). Conclusions Both on-pump and off-pump CABG are reasonable revascularization strategies in octogenarians. Careful patient selection and individualized treatment decisions can minimize postoperative mortality and morbidity in octogenarians undergoing on- and off-pump CABG.

These results demonstrate that a different genetic background is associated with physiological differences in cardiac function in vivo and differences in morphology, contractility, and Ca(2+) handling at the cellular level.

The effect of etomidate on the auditory evoked response was examined in a double-blind study carried out before the start of surgery. Fourteen patients were anaesthetized with 70% nitrous oxide and oxygen after induction with thiopentone. Ventilation was controlled. Seven of the patients received a continuous infusion of etomidate, increasing in five equal steps from 0.01 mg kg-1 min-1 to 0.05 mg kg-1 min-1 over a period of 50 min. The other seven received similarly an equivalent volume of saline. The patients given etomidate were easily distinguishable from those given saline, solely on the basis of changes in the early cortical peaks Pa and Nb. In the etomidate group the latencies of these peaks increased and their amplitudes decreased. These changes were linearly related to serum etomidate concentration. There was no effect of etomidate on the brainstem response.

In this paper, the development of a fully implantable wireless sensor able to provide continuous real-time accurate pressure measurements is presented. Surface Acoustic Wave (SAW) technology was used to deposit resonators on crystalline quartz wafers; the wafers were then assembled to produce a pressure sensitive device. Excitation and reading via a miniature antenna attached to the pressure sensor enables continuous external interrogation. The main advantages of such a configuration are the long term stability of quartz and the low power necessary for the interrogation, which allows 24/7 interrogation by means of a hand-held, battery powered device. Such data are of vital importance to clinicians monitoring and treating the effects of hypertension and heart failure. A prototype was designed and tested using both a bio-phantom test rig and an animal model. The pressure traces for both compare very well with a commercially available catheter tip pressure transducer. The work presented in this paper is the first known wireless pressure data from the left ventricle of the heart of a living swine.