Acute and chronic complications of laser angioplasty: vascular wall damage and formation of aneurysms in the atherosclerotic rabbit

Acute and chronic vascular responses to laser exposure in atherosclerotic rabbits were studied. In 7 rabbits fed an atherogenic diet for 3 to 5 months before the study to induce aortic atherosclerosis, a flexible quartz fiber, 400 micron core diameter, attached to an argon ion laser was passed anterogradely or retrogradely to the atherosclerotic ascending aorta. The laser was turned on using power intensities of 1 to 2 W for 3 seconds. After laser treatment, the aortas were studied acutely in 3 rabbits and chronically in 4 rabbits after recovery for 1 to 14 days. In 2 rabbits studied acutely, the argon laser produced a vaporized crater within the atherosclerotic plaque at the endothelial surface; however, in 1 there was also vascular damage extending deep into the medial layer. In addition, aortic aneurysm with muscular wall damage occurred in 2 of the 4 animals studied chronically. Thus, vascular complications may arise when catheter laser angioplasty is randomly applied without visualizing specific plaque targets or without using safe dose increments of power intensities and durations of exposure. This study suggests caution in the clinical use of intensive phototherapy to cardiovascular lesions and stresses the need for further understanding of laser vascular consequences before application of laser angioplasty in patients.     

The qualitative effects of laser irradiation on human arteriosclerotic disease

To determine the effects of laser irradiation upon human coronary atherosclerotic disease, coronary plaques were extracted from fresh human cadaver hearts. Seventy-four diseased artery samples were sectioned either transversely or longitudinally and subjected to laser treatment from argon-ion and carbon dioxide sources. The laser beam affected vaporization and patency in fibrous, lipoid, and calcified plaques as observed histologically. Calcified blockage showed greater extent of charred remnants following controlled thermal injury than did fibrous or lipoid obstructions. The area and depth of penetration varied directly with intensity and duration of photoirradiation and inversely with the density of the atherosclerotic tissue. This study supports further research work on the use of lasers to effect relief of atherosclerotic obstructions.     

Reduction of ventricular ectopic beats with oral acebutolol: a double-blind, randomized crossover study

The antiarrhythmic efficacy of oral acebutolol, a new cardioselective beta-blocking agent, was assessed in a randomized double-blind, placebo-controlled study. Twenty-five patients with greater than or equal to 30 ventricular ectopic beats (VEB) per hour on three control ambulatory monitorings were studied. Mean VEB reduction from the control period was 35% with placebo and 45% and 50% with the use of acebutolol 200 mg and 400 mg, respectively. Eleven patients had greater than or equal to 70% reduction in VEB with acebutolol and nine of them had greater than or equal to 90 VEB reduction. Among these 11 patients, the mean VEB suppression was 51% after placebo but significantly higher following the two doses of acebutolol at 71% (p less than 0.05) and 86% (p less than 0.01). The mean reduction of paired VEB compared to placebo was 71% (p less than 0.05) and 75% (p less than 0.01) following 200 mg and 400 mg of acebutolol and only 49% after placebo. Complete suppression of paroxysmal ventricular tachycardia was also noted in five patients. Mean PR interval only increased slightly when patients took 400 mg of acebutolol, but there was no significant change in either the QRS or QTc intervals. A significant decrease in heart rate from that during control periods was noted after acebutolol. No significant adverse reactions were noted during the study. Acebutolol appears to be an effective and well-tolerated antiarrhythmic agent in the treatment of VEB and higher grades of ventricular ectopy.     

Effects of lidocaine on hypoxic and ischemic cardiac cells

Cardiac cells severely affected by ischemia or hypoxia were exposed to lidocaineine in vitro while intracell and extracell potentials were recorded. Endocardial preparations dissected from normal dog hearts were superfused with physiologic solutions of low oxygen content until myocardial cells were partially depolarized and generated poor action potentials. Purkinje fibers were slightly altered. Epicardial preparations dissected from infarcted dog hearts to Include both normal and ischemic regions were superfused with physiologic solutions of normal oxygen content. The ischemic cells were partially depolarized and generated poor action potentials. In both types of preparations, conduction was very slow and irregular but abnormal automaticity was not observed with intracell recordings. However, abnormal spontaneous firing occurred. Lidocaineine in therapeutic concentrations (1.1 or 2.2 × 10^?5 molar) invariably abolished propagated action potentials in severely affected cells and modestly reduced membrane responsiveness in cells that were nearly normal. Concomitantly, abnormal spontaneous beats disappeared with exposure to lidocaine. The recovery of responsiveness of abnormal cells was greatly prolonged by lidocaine and strength-interval curves were shifted upward and to the right. Tetrodotoxin (5 × 10^?7 g/ml) markedly depressed or abolished the action potentials of the severely affected cells. It is concluded that lidocaine abolished abnormal spontaneous beats by extinguishing very slow conduction resulting from depressed fast channels.     

Surgical wound infection occurrence in clean operations; risk stratification for interhospital comparisons

A five year prospective study of surgical wound infection complicating eight clean elective operations was carried out in 9,108 community hospital patients by detailed stratification of risk. Remote infection, diabetes mellitus and/or operations lasting beyond 4 hours characterized high risk patients with disparate surgical wound infection rates of 1.7 percent to 7.9 percent for individual operations. Absence of these three factors defined a low risk population with statistically similar rates of 0.8 percent to 2.8 percent for the different operations, with an over-all rate of 1.5 percent. Low and high risk definitions derived from observations in eight hospitals in 1975-1977 were predictive in 12 hospitals in 1978-1979. Both classes of patients with surgical wound infection had prolonged postoperative hospitalization. Staphylococcus aureus was recovered from 50 percent of the surgical wound infections in low risk patients with hernia repair, hip fracture repair, hip prosthesis, laminectomy and mastectomy operations and from 5 percent with cesarean section, femoropopliteal bypass and hip replacement procedures (P less than 0.001). In nine high risk patients, bacteria recovered from remote infections were also present in surgical wound infections. Comparison of the occurrence of surgical wound infections in clean operations in different hospitals may be made more meaningful by stratification or risk factors and analysis of expected infecting bacteria.     

Microtransection of the His bundle with laser radiation through a pervenous catheter: Correlation of histologic and electrophysiologic data

This study describes microtransection of the His bundle with a pervenous laser catheter in a live dog. In an adult mongrel dog anesthetized with Nembutol®, administered intravenously, electrode catheters (No. 5Fr and 6Fr) were inserted through a femoral vein and positioned in the high right atrium for atrial pacing and in the His bundle region for recording of His bundle electrograms. The AH and HV intervals were measured during normal sinus rhythm and atrial pacing. Through another femoral vein, a laser fiber was inserted through a lumen catheter (No. 7Fr) with a preformed curved tip. Under fluoroscopic control, the laser fiber tip was positioned immediately next to the His bundle electrode catheter. During continuous His bundle recordings and fluoroscopic monitoring, short bursts (10 to 60 seconds) of argon laser were delivered (2.5 W) in order to produce His bundle interruption and complete heart block. Escape of a His bundle rhythm (cycle length = 1,100 ms) with QRS morphologic characteristics and duration similar to that of normal sinus rhythm was noted. “Split” His bundle potentials were recorded with an unchanged AH (50 ms) and an H'V interval of 20 ms. After the dog was killed, serial sections of the conduction system of the heart were analyzed. Histologic findings showed excellent correlation with electrophysiologic observations and validated “split” His bundle potentials. The laser radiation produced microtransection of the His bundle with a channel of tissue dissolution 0.2 to 0.3 mm wide in diameter. The latter passed through the His bundle at the junction of penetrating and branching segments, dividing it into superior and inferior portions that retained continuity with proximal and distal His bundle. Histologically, the atrioventricular node, proximal and distal His bundle segments and bundle branches were uninjured with laser radiation, and are consistent with an unchanged AH time, QRS duration and morphology. This study demonstrates that the His bundle can be precisely transected with a pervenous laser catheter technique.     

Effect of intrarenal furosemide on renal function and intrarenal hemodynamics in acute renal failure

The ability of short-term furosemide administration to alter intrarenal hemodynamics and to modify the clinical course of acute renal failure was assessed in six patients 2 to 9 days after the onset of acute renal failure. Following renal arterial catheterization, the intraarterial administration of furosemide at a dose of 9.6 mg/min for 30 minutes failed to improve renal function as assessed either by an increase in urine output or a decrease in serum creatinine during the 4 days after administration in the five oliguric patients. In a sixth patient with nonoliguric acute renal failure, urine volume increased with a gradual decrease in blood urea nitrogen and creatinine during the week after study. Furosemide failed to alter either mean renal blood flow or its intrarenal distribution as determined at intervals of 3 to 40 minutes after its infusion. These studies demonstrate that the short-term administration of furosemide in large doses does not improve renal hemodynamics or alter the clinical course of patients with established acute oliguric renal failure.     

Diagnosis of von Willebrand's disease. A comparative study of diagnostic tests on nine families with von Willebrand's disease and its differential diagnosis from hemophilia and thrombocytopathy.

Nine probands with von Willebrand's disease, and their family members, totalling 43 people, were examined. Twenty-seven had a history of bleeding; 29 had an increased factor VIII activity:factor VIII related antigen ratio; 24 had a decreased factor VIII related antigen; 23 had a prolonged bleeding time; 19 had a reduced platelet adhesiveness; 16 had a decreased factor VIII activity; and 14 had an abnormal ristocetin-induced platelet aggregation. Eight members with both normal beleeding time and normal factor VIII activity were found to have other abnormal tests: elevated ratio of factor VIII activity to factor VIII related antigen in seven; decreased factor VIII related antigen in four; and reduced platelet adhesiveness in one. Therefore, ratio of factor VIII activity to factor VIII related antigen and factor VIII related antigen are more sensitive and may be used for the detection of heterozygous carriers of von Willebrand's disease. Although patients with thrombocytopathy may have a prolonged bleeding time, decreased platelet adhesiveness and reduced platelet aggregation by ristocetin, their factor VIII activity, factor VIII related antigen and ratio of factor VIII activity to factor VIII related antigen are normal and their abnormal ristocetin test cannot be corrected by the addition of factor VIII concentrate. Hemophilic subjects and hemophilic carriers, who are deficient in factor VIII activity, usually have a normal bleeding time, normal platelet adhesiveness, and normal ristocetin test. In contrast to patients with von Willebrand's disease, their factor VIII related antigen is normal or slightly increased and their ratio of factor VIII activity to factor VIII related antigen is significantly reduced. We conclude that ratio of factor VIII activity to factor VIII related antigen and factor VIII related antigen are not only more sensitive but also more specific for the diagnosis of von Willebrand's disease.     

Electrophysiologic effects of the antiarrhythmic agent disopyramide phosphate

The electrophysiologic effects of the antiarrhythmic agent disopyramide phosphate given intravenously were studied in 10 patients with cardiac disease. Studies included determinations of sinus recovery time and refractoriness of the atria, the atrioventricular (A-V) node and the His-Purkinje system. Measurements were performed at rest and 15 and 30 minutes after administration of disopyramide. Serum drug levels were measured at these times.Sinus recovery time was shortened at both 15 and 30 minutes, with an average decrease of 39.5 and 146.2 msec, respectively (P < 0.01). Atrial refractoriness was not altered significantly, but tended to be reduced; the mean effective refractory period was 289.5 msec before administration of disopyramide and 259 and 270 msec 15 and 30 minutes, respectively, after administration. The functional refractory period of the atrioventricular (A-V) node was definitely prolonged in seven patients 15 minutes after administration of disopyramide. The relative refractory period of the His-Purkinje System was not altered.Although this study does not elucidate the mechanism by which disopyramide achieves its antiarrhythmic effects, animal work has shown that it is similar to that of quinidine. In the doses used the drug does not seem to cause first, second or third degree A-V block or fascicular or bundle branch block; it did not increase the severity of first degree A-V block in the three patients with this disturbance. The drug may be particularly useful when arrhythmias are associated with slow sinus rates.     

Atrioventricular block after reciprocating atrioventricular junctional tachycardia.

Short runs of symptomatic atrioventricular (A-V) block occurred after spontaneous cessation of reciprocating A-V junctional tachycardia in a patient with right bundle branch block, normal H-V interval and sinus nodal dysfunction. These episodes were characterized by long (more than 1 sec) P-P intervals during which the A deflections were not followed by His bundle electrograms. Three possible explanations are: (1) a posttachycardia-induced period of abnormally prolonged A-V nodal refractoriness; (2) pseudo-A-V block produced by concealed A-V junctional tachycardia, or (3) bradycardia-dependent (phase 4) A-V block at the "upper" His bundle, above the site from which the H deflection was recorded.     

Functional anatomy of the canine left bundle branch

To elucidate the architecture of the left bundle branch, activation of Purkinje (P) and myocardial (M) cells of the canine left ventricular endocardial surface was mapped in vitro before and after lesions were placed in the proximal left bundle branch. Close bipolar electrodes or microelectrodes were employed to record P and M potentials by standard techniques. The left bundle branch has conspicuous and straight border fibers that continue as bridging strands to the papillary muscles. In addition, there is a less conspicuous network of serpentine interwoven fibers in the interior of the septal portion of the bundle that has interconnections with the border fibers. Below the mid-septum and over the free wall the P fibers form a densely interwoven network. The interior septal fibers are activated nearly simultaneously with equidistant points on the border fibers. The apparent conduction velocity of the border fibers was 1.8 m/sec as opposed to 1.45 m/sec in the interior network. The bridging strands provide a shortcut across the chamber to upper portions of the free wall and septum. The pattern of activation of M cells is represented by concentric rings with an island of earliest activation (at 15 to 25 msec) in the central septum. The M cells latest to be activated are at the tips of the papillary muscles and the upper septum below the valves. Interruption of one group of border fibers may delay by 5 to 8 msec activation of P and M cells of the upper paraseptal free wall and upper septum. Lesions in the interior network delay by 2 to 4 msec activation of the P and M cells of comparatively small areas of the septum. Activation of the mid-papillary free walls, the bases of the papillary muscles and the lower septum is not affected by proximal lesions partially interrupting the bundle branch. Transection of both groups of border fibers does not produce complete block. The left bundle branch is best represented as a fan-shaped network of interwoven fibers whose diverging border fibers are specialized for rapid, distant transport.     

Benign primary hematuria. Clinicopathologic study of 65 patients.

Renal biopsy specimens were examined in a group of 65 patients with primary hematuria who met the following criteria: urine protein excretion under 1 g in 24 hours or a negative Albustix^® in a concentrated specimen, absence of hypertension and normal renal function. The median age at discovery of the disease was 13 years, and the median duration of the hematuria at biopsy was two years. Recurrent gross hematuria was present in 38 instances. Thirty of the 65 renal biopsy specimens showed mesangial proliferative glomerulonephritis and in 44 there were red blood cells in the tubules. Mesangial deposits of a variety of immunoglobulins and/or third component of complement (C3) were identified in 30 of the 44 biopsy specimens examined. Immunoglobulin M (IgM) was the predominant immunoglobulin. Electron dense mesangial deposits were identified only in 12 cases; however, ultrastructural study of the biopsy specimens led to the detection of one patient who was probably suffering from Alport's syndrome. There was a poor correlation between histologic lesions and immunohistochemical findings. Thirty-nine patients were followed for a median period of four years without evidence of any deterioration of renal or any other manifestation of renal or systemic disease, although half of these patients still showed bleeding in the last urinalysis. Thus, the name benign primary hematuria appears appropriate to designate this clinical syndrome. The use of pathologic terms such as focal glomerulonephritis or immunoglobulin A (IgA) nephropathy (Berger's disease) has been a cause of ambiguity since there is not a consistent correlation between these lesions and clinical manifestations. Because the discrete mesangial changes may be predicted virtually from the clinical presentation, kidney biopsy may not seem to be indicated in the majority of these patients unless there is an increase in urinary protein excretion or other manifestations of renal, genitourinary or systemic disease appear.     

Renal acidosis and renal potassium handling in selective hypoaldosteronism

Selective hypoaldosteronism was demonstrated in a 60 year old black man with moderate renal insufficiency and hyperkalemic, hyperchloremic acidosis. Urine pH was appropriately low during acid loading demonstrating that the hydrogen ion gradient generating capability of the distal-most nephron was intact. In addition to impaired net acid excretion during acidosis, significant bicarbonaturia was present when serum bicarbonate concentration was normal. Desoxycorticosterone acetate (DOCA) administration improved renal potassium handling and corrected the hyperkalemia but not the acidosis or bicarbonaturia.It is concluded that the patient had idiopathic selective hypoaldosteronism and hyporeninemia and that the hyperkalemia was related to hypoaldosteronism. The patient's bicarbonaturia, however, did not appear to be related to mineralocorticoid deficiency and therefore should be attributed to other factors.     

Effects of carbon dioxide, Nd-YAG, and argon laser radiation on coronary atheromatous plaques

Laser radiation has been successfully applied in several areas of medical practice. However, its use in cardiology and specifically its effects on obstructive atherosclerosis have largely been unexplored. To evaluate effects of laser radiation on atherosclerotic plaques 25 fresh necropsy atherosclerotic coronary artery segments were exposed to laser radiation with either a carbon dioxide, Nd-YAG, or argon laser. Split or intact segments were prepared under dry conditions or while immersed in saline solution or blood and exposed to laser radiation as power and duration of exposure varied. All 3 lasers were capable of creating controlled injury to atherosclerotic plaques. In general, the magnitude of injury varied according to the total energy delivered (that is, power times duration of exposure). Calcified and noncalcified plaques were penetrated with similar levels of injury. Histologic examination demonstrated that laser radiation produced a wedge incision in the atherosclerotic plaque which was surrounded by zones of thermal and acoustic injury.     

Experimental coronary arterial occlusion and release: Effects on enzymes,electrocardiograms, myocardial contractility and reactive hyperemia

After less than 1 hour of coronary arterial occlusion, the myocardium suffers irreversible changes as revealed by electron microscopy. Yet, the earliest clinical laboratory indexes of myocardlal infarction—elevated serum enzyme levels and significant Q waves on the electrocardiogram—are not detected until at least 6 hours after coronary occlusion. To study the early period after coronary occlusion in the dog, occlusion of the left anterior descending coronary artery for 1 to 3 hours was followed by release, and coronary sinus and venous enzyme levels, the electrocardiogram and myocardial contractility from the infarcted area, and reactive hyperemia were monitored. Coronary sinus enzyme levels rose within 15 minutes after release of occlusion in half of the experiments with $\text{1}\text{to}\text{1}\text{1}\text{2}$ hours and in all of those with 2 to 3 hours of occlusion, and this rise preceded the rise in venous levels by only 10 to 20 minutes. Significant Q waves appeared 15 to 30 minutes after release of occlusion as the serum enzymes were increasing. Thus, clinically, the delayed appearance of increased serum enzymes and significant electrocardiographic Q waves is probably largely due to a lack of circulation in the infarcted area rather than to prolonged survival time. Also, the venous enzyme level reflects the coronary sinus level minutes later. The presence of viable myocardium in the infarcted area was suggested by elevation of the S-T segment upon reclamping, and by residual myocardial contractility and retained capacity for reactive hyperemia. These findings occurred in some experiments even In the presence of a significant Q wave.