Transcutaneous electrical nerve stimulation as a novel method of remote preconditioning: in vitro validation in an animal model and first human observations.

Remote ischemic preconditioning (rIPC) induced by transient limb ischemia (li-rIPC) leads to neurally dependent release of blood-borne factors that provide potent cardioprotection. We hypothesized that transcutaneous electrical nerve stimulation (TENS) is a clinically relevant stimulus of rIPC. Study 1: seven rabbits were subjected to lower limb TENS; six to li-rIPC, and six to sham intervention. Blood was drawn and used to prepare a dialysate for subsequent analysis of cardioprotection in rabbit Langendorff preparation. Study 2: 14 healthy adults underwent upper limb TENS stimulation on one study day, 10 of whom also underwent li-rIPC on another study day. Blood was drawn before and after each stimulus, dialysate prepared, and cardioprotective activity assessed in mouse Langendorff preparation. The infarct size and myocardial recovery were measured after 30 min of global ischemia and 60 or 120 min of reperfusion. Animal validation: compared to control, TENS induced marked cardioprotection with significantly reduced infarct size (TENS vs. sham p < 0.01, rIPC vs. sham p < 0.01, TENS vs. rIPC p = ns) and improved functional recovery during reperfusion. Human study: compared to baseline, dialysate after rIPC (pre-rIPC vs. post-rIPC, p < 0.001) and TENS provided potent cardioprotection (pre-TENS vs. post-TENS p < 0.001) and improved myocardial recovery during reperfusion. The cardioprotective effects of TENS dialysates were blocked by pretreatment of the receptor heart with the opioid antagonist naloxone. TENS is a novel method for inducing cardioprotection and may provide an alternative to the limb ischemia stimulus for induction of rIPC clinically.

Electroacupuncture reduces myocardial infarct size and improves post-ischemic recovery by invoking release of humoral, dialyzable, cardioprotective factors.

Previous studies have shown that electroacupuncture (EA) can induce cardioprotection against ischemia-reperfusion (IR) injury, but its mechanisms are incompletely understood. We have previously shown that several other forms of remote preconditioning of the heart work, at least in part, via the release of circulating cardioprotective factors into the bloodstream, that can be dialyzed and subsequently shown to reduce IR injury in isolated hearts. We used the same methods to assess whether EA leads to similar humoral cardioprotection. EA rabbits were subjected to 60 min of bilateral stimulation at the Neiguan point, following which their blood was drawn, dialyzed, and used to perfuse hearts in Langendorff preparation and subsequently subjected to 60 min of global ischemia and 120 min of reperfusion. Compared to controls, dialysate from EA animals led to significant reduction in infarct size and improved functional recovery. The degree of cardioprotection was no different to that seen in animals randomized to receive remote preconditioning using transient limb ischemia (4 cycles of 5 min ischemia/5 min reperfusion). These results suggest that EA recapitulates the cardioprotection achieved by remote preconditioning, by similarly leading to release of circulating cardioprotective factors.

Epinephrine increases mortality after brief asphyxial cardiac arrest in an in vivo rat model.

Epinephrine may be detrimental in cardiac arrest. In this laboratory study we sought to characterize the effect of epinephrine and concomitant calcium channel blockade on postresuscitation myocardial performance after brief asphyxial cardiac arrest. Anesthesized rats were disconnected from mechanical ventilation, resulting in cardiac arrest. Resuscitation was attempted after 1 min with mechanical ventilation, oxygen, chest compressions, and IV medication. In experimental series 1 and 2, animals were allocated to 10 or 30 microg/kg epinephrine or 0.9% saline. In series 3, animals received 30 microg/kg of epinephrine and were randomized to 0.1 mg/kg of verapamil or to 0.9% saline. In series 1 and 3, left ventricular function was assessed using transthoracic echocardiography. In series 2, left atrial pressure was measured. Epinephrine was associated with increased mortality (0/8 [0%] in controls, 4/12 [33.3%] in 10 microg/kg animals, and 16/22 [72.8%] in 30 microg/kg animals; P < 0.05), hypertension (P < 0.001), tachycardia (P = 0.004), early transient left atrial hypertension, and dose-related reduction in left ventricular end diastolic diameter (P < 0.05). Verapamil prevented mortality associated with large-dose epinephrine (0% versus 100%) and attenuated early diastolic dysfunction and postresuscitation hypertension (P = 0.001) without systolic dysfunction. Epinephrine appears to be harmful in the setting of brief cardiac arrest after asphyxia.

Validation of myocardial acceleration during isovolumic contraction as a novel noninvasive index of right ventricular contractility: comparison with ventricular pressure-volume relations in an animal model.

BACKGROUND: We have demonstrated that myocardial acceleration during isovolumic contraction (IVA) is a sensitive index of left ventricular contractile function. In this study, we assessed the utility of IVA to measure right ventricular (RV) contractile function. METHODS AND RESULTS: We examined 8 pigs by using tissue Doppler imaging of the RV free wall and simultaneous measurements of intraventricular pressure, volume, maximal elastance (e(max)), preload recruitable stroke work, and dP/dt(max) by conductance catheterization. Animals were paced in the right atrium at a rate of 130 beats per minute (bpm). IVA was compared with elastance during contractility modulation by esmolol and dobutamine and during preload reduction and afterload increase by transient balloon occlusion of the inferior vena cava and pulmonary artery, respectively. Data were also obtained during incremental atrial pacing from 110 to 210 bpm. Esmolol led to a decrease in IVA and dP/dt(max). During dobutamine infusion, IVA, dP/dt(max), preload recruitable stroke work, and e(max) all increased significantly. During preload reduction and afterload increase, IVA remained constant up to a reduction of RV volume by 54% and an RV systolic pressure increase of 58%. Pacing up to a rate of 190 bpm led to a stepwise increase in IVA and dP/dt(max), with a subsequent fall at a pacing rate of 210 bpm. CONCLUSIONS: IVA is a measurement of RV contractile function that is unaffected by preload and afterload changes in a physiological range and is able to measure the force-frequency relation. This novel index may be ideally suited to the assessment of acute changes of RV function in clinical studies.