Responses to Norepinephrine of Normal and "Ischemic" Canine Purkinje Fibers are Consistent with Activation of Different α1-Receptor Subtypes

α₁-Receptor Subtype Stimulation of Purkinje Fibers. Introduction: Previously we found that WB4101 (WB) 10^-7 M competitively blocks three α₁-adrenergic receptor-effector responses: the increase in normal automaticity occurring in Purkinje fibers (PF) at high membrane potentials: the increase in abnormal automaticity occurring in PF at depolarized membrane potentials; and the prolongation of PF action potential duration. These observations are consistent with two different hypotheses: (1) WB blocks a single α₁-receptor subtype, which subserves different effector pathways; and (2) WB blocks different receptor subtypes, eacb of which subserves an independent patbway. The aim of this study was to test both hypotheses. Methods and Results: We used standard microelectrode techniques to study the concentration-dependent actions of three α₁-adrenoreceptor blockers (WB (α_1A?α_1D], 5-methylurapidil [5-MU] [α_1A, ?α_1D], and UK52,046 [nonselective]) on norepinephrine (NK) effects in normal PF and in PF depolarized with a simulated ischemic solution ([K⁺]_o= 10 mM; pO₂ < 20 mmHg; pH 6.8; maximum diastolic potential -60 ± 1 mV). In normally polarized PF, concentration-dependent actions of all blockers on both the positive cbronotropic response and the prolongation of action potential duration completely coincide. In contrast, the response to NE of abnormal automaticity in “ischemic” PF differs from normals: there is a bigh sensitivity to WB and 5-MU and no response to UK52,046. Conclusions: (1) A single receptor subtype appears responsible for botb the α₁-induced prolongation of repolarization and the positive chronotropic effect in normal PF. (2) Two different receptor subtypes may be responsible for the α₁-induced effects on automaticity in normal and ischemic fibers. It is likely that the latter one is α_1A, and that consideration of antiarrhythmic therapy with α₁-adrenergic blockers should focus on this subtype as a potential target.     

Transcoronary Venous Radiofrequency Catheter Ablation of Ventricular Tachycardia

Coronary Venous Ablation of VT. Ventricular tachycardias in coronary artery disease arise mostly from endocardial sites. However, little is known about the site of origin in other diseases. We present the case of an incessant, adenosine-sensitive ventricular tachycardia arising from the lateral wall of the left ventricle in a patient with mildly reduced left ventricular function. Intracardiac mapping suggested an epicardial origin, and the tachycardia was successfully ablated from a coronary sinus branch. After ablation, left ventricular function returned to normal. Transcoronary venous radiofrequency catheter ablation is a new approach for the treatment of ventricular tachycardia. Its value in the management of other types of ventricular tachycardia has yet to he determined.     

Analysis of heat-shock protein expression in myeloid leukaemia cells by flow cytometry

Expression of heat-shock proteins (hsp) was analysed in the leukaemic cells of 12 patients with acute myeloid leukaemia (AML) and nine patients with chronic myeloid leukaemia (CML). Using monoclonal antibodies to hsp70, hsp90 and hsp60 (ML30, a mycobacterial antigen with homology to human hsp60), we measured hsp levels by flow cytometry of permeabilized cells. Mononuclear cells from 10 healthy volunteers were also examined. The results demonstrate that hsp expression is significantly increased (P<0'01) in the circulating cells of patients with AML compared with cells from CML patients, and compared with normal peripheral blood mononuclear cells. This increased pattern of expression was found for all three heat-shock protein families included in this study. Mononuclear cells from leukaemic patients showed a heterogenous pattern of hsp expression, between different patients, between cells from individual patients, and between the different hsp proteins examined. It is possible that hsp expression relates to the differentiation state or proliferative potential of these leukaemic cells.     

Stem Cell Migration and Proliferation During Severe Anemia

The pluripotential stem cell (CFU) compartment of marrow and spleen wasevaluated in mice subjected to an intense erythroid stimulus associated withphenylhydrazine-induced anemia. Erythroid hyperplasia occurred in both marrow and spleen. CFU in the marrowgradually declined to approximately 50per cent of control levels (day 5) whiletheir numbers in the spleen increased(fourfold) by day 3 and were maintainedat this level for several days. Thesechanges in numbers of marrow andsplenic CFU were not associated withCFU proliferation. Thereafter, CFU inthe marrow, but not in the spleen, entered active cell cycle. The data suggestthat CFU migrate from marrow to spleenduring the demands of severe anemia.The induction of marrow CFU into cyclefurther suggests a negative feedback,which, perhaps through cell-cell interaction, maintains stem cells at a criticalcompartment size. The failure of splenicCFU to cycle may reflect the converseeffect, i.e. an inhibition on stem cell proliferation in the wake of an expandedstem cell pool.

Submitted on March 17, 1970 Revised on May 14, 1970 Accepted on June 9, 1970     

Arteriovenous Malformation of the Stomach

Of the multitude of sources capable of producing massive hemorrhage from the gastrointestinal tract, one of the rarest forms is arteriovenous malformation (AVM) of the stomach. The typical patient is a middle-aged male who presents with recurrent painless massive hematemesis and an unremarkable past medical history. Until recently the diagnostic work-up has often presented a dilemma, with the lesion rarely being confirmed prior to laparotomy. The patient whom we have encountertd with AVM of the stomach confirms our belief in the use of visceral angiography as a vital tool in the diagnosis of obscure gastrointestinal bleeding. We present this case as one which is unusual in its diagnostic work-up, therapeutic approach and pathologic findings.     

Atrial Support Pacing in Heart Failure: Results from the Multicenter PEGASUS CRT Trial

Atrial Pacing in Heart Failure. Introduction: Cardiac resynchronization therapy (CRT) efficacy trials to date used atrial‐synchronous biventricular pacing wherein there is no or minimal atrial pacing. However, bradycardia and chronotropic incompetence are common in this patient population. This trial was designed to evaluate the effect of atrial support pacing among heart failure patients receiving a CRT defibrillator. Methods and Results: PEGASUS CRT was a multicenter, 3‐arm, randomized study. At 6 weeks, patients were randomized to DDD mode at a lower rate of 40 bpm (DDD‐40; control arm), or one of the following 2 treatment arms: DDD‐70, or DDDR‐40. The primary endpoint was a clinical composite endpoint that included all‐cause mortality, heart failure events, NYHA functional class, and patient global self‐assessment. Subjects were classified as improved, unchanged, or worsened at 12 months. There were 1,433 patients randomized, of whom 66% were male, mean age was 67 ± 11 years, and mean left ventricular ejection fraction was 23 ± 7%. The average follow‐up time was 10.5 ± 3.5 months and 1,309 patients contributed to the primary endpoint. No significant differences were observed in the composite endpoint between either of the 2 treatment arms compared to the control arm (P>0.05 for both comparisons). Additionally, there were no differences among the groups in mortality or heart failure events. Conclusion: In advanced heart failure patients treated with CRT, atrial support pacing did not improve clinical outcomes compared to atrial tracking. However, atrial pacing did not adversely affect mortality or heart failure events. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1317‐1325, December 2012)     

Advanced interventional pulmonology procedures: Training guidelines from the Thoracic Society of Australia and New Zealand

Training in interventional pulmonology procedures is increasing in popularity. However, the nature of training is difficult to define, particularly with respect to an adequate number of cases. These guidelines approach training not just from a modest number of supervised cases, but also from a range of educational and outcome targets which give a rounded approach to the issue. These include prerequisite skills from basic procedures, the place of simulated training, formal simulation testing, modest procedural outcome and side effect targets, audit presentations, ongoing reading, and hands‐on training expectations. All of this would still be under the supervision of an experienced trainer.