Permanent His Bundle Pacing in Intra-Hisian Conduction Block: Mechanistic Insights.

We are reporting a patient with discrete intra-His conduction block and describe a refined technique of permanent His bundle pacing assuring reliable ventricular capture. Meticulous mapping of the site of block with lead placement distal to the site of block and non-selective His bundle pacing with local myocardial capture as an additional safety back up appears to be the technique of choice.

An apoptosis signal-regulating kinase 1 inhibitor reduces cardiomyocyte apoptosis and infarct size in a rat ischemia-reperfusion model.

PURPOSES: We determined whether a small molecule inhibitor of apoptosis signal-regulating kinase 1 (ASK1-i) could reduce myocardial infarct size in a rat ischemia/reperfusion model. METHODS AND RESULTS: Sprague-Dawley rats were randomized to 3 groups: ASK1-i infusion (n = 16), vehicle infusion (n = 16), or ischemic preconditioning (IPC; n = 15). Infusion of ASK1-i (10 mg/kg, iv) or vehicle commenced 45 minutes before myocardial ischemia. IPC consisted of 3 cycles of 3 minutes of coronary occlusion followed by 5 minutes of reperfusion immediately before index myocardial ischemia, which consisted of 30-minute left coronary occlusion followed by 180 minutes of reperfusion. Pathologic analysis revealed no significant difference in the ischemic risk size among the 3 groups. ASK1-I and IPC significantly reduced myocardial infarct size (27.7% ± 3.3%, 16.5% ± 3.4%, and 41.5% ± 4.8% in the ASK1-i group, the IPC group, and the vehicle group, respectively; P = 0.0002) and apoptosis (the percentage of apoptotic nuclei averaged 11.6% ± 1.0%, 10.2% ± 1.7%, and 17.7% ± 2.0% in the ASK1-i group, IPC group, and vehicle group, respectively, P = 0.0055). CONCLUSIONS: A small molecule inhibitor of ASK1 was shown for the first time to reduce apoptosis and myocardial infarct size in a rat model of ischemia/reperfusion.

Compartment syndrome caused by computed tomography contrast infiltration seen on a Tc-99m methylene diphosphonate bone scan.

A 72-year-old man was hospitalized for transurethral resection of bladder cancer. Two days after the procedure, the patient continued to have gross hematuria and a computed tomography (CT) scan of the abdomen and pelvis with intravenous contrast was performed to check the integrity of the resection site. Later that day, the patient underwent technetium-99m methylene diphosphonate (MDP) bone scintigraphy to investigate the possibility of bone metastasis. The bone scan showed no signs of metastasis but did reveal increased uptake of the left hand and forearm on the opposite side of the injection site.

Combined remote perconditioning and postconditioning failed to attenuate infarct size and contractile dysfunction in a rat model of coronary artery occlusion.

OBJECTIVE: Although preconditioning remains one of the most powerful maneuvers to reduce myocardial infarct size, it is not feasible in the clinical setting to pretreat patients prior to acute myocardial infarction (MI). The purpose of this study was to investigate the effect of more clinically relevant therapies of remote perconditioning, postconditioning, and the combined effect of remote perconditioning and postconditioning on myocardial infarct size in an anesthetized rat model. METHODS: Anesthetized rats were subjected to 45 minutes of proximal left coronary artery occlusion followed by 2 hours of reperfusion. Remote perconditioning was performed 5 minutes after left coronary occlusion with 4 cycles of 5 minutes of occlusion and reperfusion of both the femoral arteries. Postconditioning was applied immediately prior to 2 hours of full reperfusion with 6 cycles of 10 seconds occlusion-reperfusion of the coronary artery. The combined effect was produced by preceding the postconditioning regimen with remote perconditioning, after 5 minutes of left coronary occlusion. RESULTS: Remote perconditioning and postconditioning alone failed to reduce infarct size expressed as percentage of the risk zone (42.2% ± 3.9% and 45.0% ± 4.3%). The combination of remote perconditioning and postconditioning also failed to reduce infarct size (45.3% ± 4.1%) as compared to the untreated ischemia-reperfusion group (48.7% ± 3.4%). Hemodynamics including left ventricular end-systole and end-diastolic pressures, +dP/dt, -dP/dt, and heart rate did not show any improvement in the conditioning groups. CONCLUSION: This study shows that remote perconditioning and postconditioning alone or combined neither improve hemodynamics nor reduce infarct size in the rat model of MI.

An update on cardioprotection: a review of the latest adjunctive therapies to limit myocardial infarction size in clinical trials.

Acute myocardial infarction (AMI) with subsequent left ventricular dysfunction and heart failure continues to be a major cause of morbidity and mortality in the Western world. Rapid advances in the treatment of AMI, mainly through timely reperfusion, have substantially improved outcomes in patients presenting with acute coronary syndrome and particularly ST-segment elevation myocardial infarction. A vast amount of research, both translational and clinical, has been published on various pharmacological and interventional techniques to prevent myocardial cell death during the time of ischemia and subsequent reperfusion. Several methods of cardioprotection have shown the ability to limit myocardial infarction size in clinical trials. Examples of interventional techniques that have proven beneficial are ischemic post-conditioning and remote ischemic per-conditioning, both of which can reduce infarction size. Lowering core body temperature with cold saline infusion and cooling catheters have also been shown to be effective in certain circumstances. The most promising pharmaceutical cardioprotective agents at this time appear to be adenosine, atrial natriuretic peptide, and cyclosporine, with other potentially effective medications in the pipeline. Additional pre-clinical and clinical research is needed to further investigate newer cardioprotective strategies to continue the current trend of improving outcomes following AMI.

Protecting the heart from ischemia: an update on ischemic and pharmacologic conditioning.

The attempt to find treatments that will reduce myocardial cell death during periods of ischemia and subsequent reperfusion has spanned nearly 40 years. Although many therapies have shown promise in animal models, relatively few have been successful in clinical trials. Some of the most effective clinical therapies involve techniques designed to elicit the heart's own innate capacity to protect itself. The ability of the heart to render itself more resistant to ischemia/reperfusion injury was not appreciated until the description of ischemic preconditioning in 1986. Following the discovery that brief, nonlethal episodes of ischemia conditioned the heart to better tolerate a subsequent prolonged episode of ischemia, alternative ways of evoking this endogenous cardioprotection were described. Ischemic postconditioning and remote conditioning are potentially useful tools for protecting ischemic myocardium, and have been shown to be beneficial in small clinical trials. Several pharmacologic agents have the ability to mimic the effects of ischemic conditioning and can also reduce the amount of cell death during ischemia/reperfusion. This article provides the clinician with an overview of the different techniques of ischemic conditioning and how they can protect the myocardium from ischemia/reperfusion injury. Additionally, several pharmacologic agents that can protect the heart in a similar manner are discussed.