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Biomedical subjects

J E Lowe

Publications and source records attributed to J E Lowe.

At least 163 records · Page 9Linked to original sources

The effect of chemical ablation of the endocardium on ventricular fibrillation threshold.

The purpose of this study was to examine the effects of ablation of the superficial endocardium and Purkinje network on left ventricular fibrillation threshold. Lugol's solution was applied through small ventriculotomies to the left and right ventricular endocardium of 10 dogs on cardiopulmonary bypass. Two control groups of five animals each underwent either endocardial application of saline or epicardial application of Lugol's solution. Ventricular fibrillation threshold was measured before and after each intervention by the single-stimulus technique. Application of Lugol's solution to the endocardium resulted in a 102 +/- 15% increase in ventricular fibrillation threshold from a control value of 26 +/- 2 to 53 +/- 6 mA (p less than .005). In two animals, ventricular fibrillation could not be initiated postoperatively. In the control groups, there were no significant changes in ventricular fibrillation threshold. Histologic examination revealed that Lugol's solution obliterated less than 0.5 mm of superficial endocardium while sparing the adjacent myocardium. Electrophysiologic and rheologic data confirmed the discrete nature of the chemical injury. Thus ablation of the superficial ventricular endocardium with Lugol's solution results in a profound increase in the ventricular fibrillation threshold with only minimal tissue destruction.

Animals↗

Protective metabolic effects of propranolol during total myocardial ischemia.

Clinical trials have shown an increase in survival in patients treated with beta blockers after infarction. In addition, the majority of patients undergoing myocardial revascularization are also treated preoperatively with beta blockers. It is commonly thought that beta blockers exert their protective effect primarily by decreasing heart rate and subsequent myocardial work. The present study was designed to determine whether beta blockade has any primary protective metabolic effects on globally ischemic myocardium. Thirty-four anesthetized dogs underwent total myocardial ischemia at 37 degrees C. High-energy nucleotide and lactate levels in left ventricular tissue samples were determined at control and at 15 minute intervals as well as at the onset of ischemic contracture in 24 dogs. Seventeen dogs were treated with propranolol before ischemia. The time to ischemic contracture in control dogs was 63.3 +/- 1.4 minutes compared with 75.9 +/- 2.2 minutes in the propranolol-treated group (p less than 0.01). In addition to significantly delaying the onset of ischemic contracture, propranolol also decreased the rate of anaerobic glycolysis during ischemia. Ischemic contracture occurred in the control group with an average adenosine triphosphate level of 1.26 +/- 0.08 mumol compared to 0.91 +/- 0.08 mumol/gm wet weight for the beta blocked group (p less than 0.0025). These are the first data suggesting that the protective effects of beta blockade may be related to a beneficial effect on ischemic myocardial metabolism allowing myocardium to survive with lower levels of adenosine triphosphate.

Adenine Nucleotides↗

Normal motility of the cecum and right ventral colon in ponies.

To study the normal motility of the cecum and right ventral colon (RVC) in 3 mature Shetland ponies, a 6-part, indwelling, intraluminal catheter system was used to measure intraluminal pressure changes. Three catheters were placed in the cecum at 10, 25, and 40 cm from the cecocolic orifice, and 3 catheters were placed in the RVC at 10, 20, and 30 cm from the cecocolic orifice. Recordings were made during the interdigestive period beginning 2 weeks after surgical operation was done. Frequent, low-amplitude peaks (0.35 +/- 0.13 coordinated peaks/min) were seen involving the cecal body and caudal cecal base, which represented a haustra-to-haustra mixing pattern. Coordinated pressure peaks originated in the cecal body and progressed to the cranial cecal base (0.07 +/- 0.01/min) or originated in the cranial cecal base and progressed to the cecal body (0.07 +/- 0.04/min). Associated with a loud rush of ingesta heard on transabdominal auscultation and progression of liquid ingesta confirmed with barium contrast radiography, there was a series of coordinated, progressive pressure peaks which originated in the cecal body, sequentially involved the cecal base, traversed the cecocolic orifice, and extended into the RVC (0.36 +/- 0.05/min). It seemed that a pacemaker region existed in the cecal body and initiated the important aborally propagated progressive pattern responsible for the transit of ingesta from the cecum to the RVC. A separate mechanism for the transit of gas was not identified. In the RVC, infrequent, nondirectional, low-amplitude segmental pressure peaks (0.12 +/- 0.06/min), and aborally progressive coordinated pressure peaks originating at the beginning of the RVC (0.09 +/- 0.02/min), occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of acute tachycardia on left ventricular adenine nucleotide levels and subsequent tolerance to ischemia.

Electrophysiologically guided surgical procedures for the ablation of supraventricular and ventricular dysrhythmias often require prolonged periods of tachycardia to complete intraoperative mapping studies. It is unknown whether tachycardia depletes the myocardium of high-energy compounds or alters subsequent tolerance to ischemia. In the present study, 12 anesthetized dogs were paced from the right ventricle at a cycle length of 250 msec for 60 minutes. In seven animals, drill biopsy specimens were taken from the left ventricular free wall for analysis of adenine nucleotide levels and their breakdown products before and after pacing and after 20 minutes of recovery from pacing. In the remaining five animals, the heart was made totally ischemic immediately after tachycardia and the time to the onset of ischemic contracture was determined and compared to that of five nonpaced control dogs. Acute tachycardia resulted in no significant reduction in adenine nucleotide levels compared to control values. Furthermore, in hearts rendered totally ischemic after tachycardia, the mean time to ischemic contracture was 65.6 +/- 1.3 minutes versus 63.6 +/- 2 minutes in nonpaced control animals (no significant difference). These data show that pacing-induced tachycardia in the normal heart does not decrease adenine nucleotide levels or affect subsequent tolerance to ischemia. These results may be clinically relevant to patients without coronary artery disease who undergo operative procedures necessitating prolonged periods of tachycardia for intraoperative mapping to identify the site of arrhythmogenesis.

Adenine Nucleotides↗

Transient assay, by [3H]guanine incorporation of Escherichia coli xanthine-guanine phosphoribosyl transferase (GPT) in transfected human fibroblasts.

We have used [3H]guanine incorporation as a rapid and sensitive assay of xanthine-guanine phosphoribosyl transferase (GPT) activity in SV40 transformed human fibroblasts. The SV40 early promoter is more efficient than the Rous sarcoma virus long terminal repeat for transient expression of the gpt gene. The assay works well in a derivative of AT5BIVA which lacks hypoxanthine-guanine phosphoribosyl transferase (hprt-) and we show here how the assay has been adapted to work in the hprt+ AT5BIVA parent.

Ataxia Telangiectasia↗

Ultrasound diagnosis of pseudoaneurysm and contiguous ventricular septal defect complicating inferior myocardial infarction.

Two patients with recent inferior myocardial infarction were found by two-dimensional and Doppler echocardiography to have both an inferior wall pseudoaneurysm and a contiguous rupture of the posterior ventricular septum. The pseudoaneurysm was not suspected clinically in either patient. In one patient, a complex or dissecting septal rupture was visualized in detail. To our knowledge, the combined defect has not previously been diagnosed during life by noninvasive methods.

Aged↗

Distribution of substance P-like immunoreactivity in the enteric neurons of the large colon of normal and amitraz-treated ponies: an immunocytochemical study.

The distribution of the putative motor excitatory neurotransmitter, substance P, was studied immunocytochemically in the left dorsal colon of four normal control ponies and three ponies with amitraz-induced impaction colic. Substance P-like immunoreactivity in the control ponies was observed in nerve fibres in all layers of the bowel wall and in the nerve cell bodies of the enteric ganglia. The substance P-like immunoreactivity was clearly more intense in the cell bodies of submucosal ganglia than in those of the myenteric ganglia. The internodal nerve strands of the myenteric plexus were very rich in substance P-like immunoreactivity and within the ganglia they formed dense varicose networks around the neuronal cell bodies. Nerve bundles rich in substance P-like immunoreactivity diverged inward from the myenteric plexus to contribute an abundance of varicose immunoreactive fibres to the circular muscle of the tunica muscularis. Nerve fascicles with substance P-like immunoreactivity were sparse in the longitudinal muscle except in the thickened taenial band. In the submucosa many of the nerve fibres with substance P-like immunoreactivity appeared to arise from ganglionic cell bodies. Immunoreactive fibres commonly condensed around arterial vessels in the submucosa. Fine immunoreactive nerve fascicles from the submucosal plexus also projected internally to supply the muscularis mucosae and form periglandular arrays in the lamina propria. The distribution of substance P-like immunoreactivity in the normal equine colon differed in some respects from patterns observed in large intestines of other mammals. When the colons of normal and amitraz-treated ponies were compared no differences were discerned in the distribution or intensity of substance P-like reactivity.

Animals↗

Trials of serotonin, substance P and alpha 2-adrenergic receptor effects on the equine large colon.

Some support for both serotonin and substance P as biotransmitters in the equine large colon is presented. Close arterial injections of small quantities of each of these were effective, respectively, in stimulating marked increases in coordinated pressure peaks in the vicinity of the pelvic flexure, with modest (serotonin) or marked (substance P) increase in colon artery blood flow. Both the acaricide, amitraz, and the tranquilizer xylazine appeared to act on the equine large colon via yohimbine-sensitive alpha 2-adrenergic receptors.

Animals↗

An attempt to transfer radiation resistance to an ataxia-telangiectasia cell line.

Fibroblasts from ataxia-telangiectasia (AT) are hypersensitive to the lethal effects of ionizing radiation. Genomic DNA from normal human cells was transfected together with the selectable bacterial marker, gpt, on plasmid pSV2 into an SV40-transformed AT line, AT5BIVA. One radiation resistant clone (67) was recovered following repeated cycles of gamma-irradiation from a population of 90,000 clones. The normal level of radiation resistance has been maintained for at least 11 months in the absence of further selection by radiation. The resistant clone is not a contaminant as determined by isoenzyme analysis, carries one copy of the gpt gene, and its DNA synthesis is inhibited after radiation to an extent intermediate between that of AT and normal cells. It is not yet established whether clone 67 is a bona fide transformant or arose as a consequence of mutation of the parent AT line.

Ataxia Telangiectasia↗

Fatigue characteristics and biocompatability of a totally implantable bone growth stimulator in ponies.

Materials fatigue and gross biocompatability of an implantable bone growth stimulator (BGS) were assessed in a 6-month trial using 6 ponies. The forelegs of each pony were implanted with a BGS; the right leg implant had the cathode and cathode lead preconnected by the manufacturer, and the left leg implant was connected at surgery. Evaluation was by radiographic and clinical examination at the beginning and end of the experimental period. Six of the 12 cathode leads (50%) and 7 of the 12 cathodes (58%) were broken at 6 months. All of the implanted preconnected cathode and insulated cathode leads and 33.3% of the surgically connected cathodes and insulated cathode leads were connected at the titanium connector socket at 6 months. This BGS may exhibit wire fatigue greater than 50% of the time when used in the distal extremity of the horse.

Animals↗

Pneumopericardium resulting in cardiac tamponade.

Cardiac tamponade most commonly results from accumulation of blood or other fluids within the pericardial sac. However, there is a growing body of clinical evidence showing that pneumopericardium can lead to cardiac tamponade in a large number of patients. Including those in the present report, a total of 252 patients with pneumopericardium are available for review. Interestingly, cardiac tamponade developed in 94 patients, or 37% of this group, because of air within the pericardial space. Pneumopericardium resulting in tamponade most frequently occurs in trauma patients or in newborn infants requiring positive pressure ventilation. This syndrome can be recognized promptly because of its characteristic physical findings and radiographic features. Although air tamponade can be treated effectively by either needle aspiration or insertion of a pericardial tube, the development of a pneumopericardium is a bad prognostic sign. Out of the 221 patients reported in the literature whose outcome is known, 127 (57%) died. In the group with a tension pneumopericardium, the mortality was 56% (53 out of 94 patients). Even without the development of tension, however, pneumopericardium was associated with a 58% mortality (74 out of 127 patients) due to other underlying disease processes.

Adult↗

Clinical characteristics and current management of medically refractory unstable angina.

Of 531 patients admitted to the Duke Coronary Care Unit with unstable angina (UA) from June 1981 to September 1982, 100 had persistent angina despite optimal medical therapy of nitrates, propranolol, and nifedipine. At catheterization, 70% of the refractory patients had left main (LM) or three-vessel disease (TVD), 68% had left ventricular end-diastolic pressures of greater than 12 mmHg, and 24% had ejection fractions (EF) of less than 0.40. Twenty-four patients were greater than 65 years of age, and 53 had associated major diseases. Forty-eight patients (Group I) had no evidence of myocardial infarction in the 30 days before catheterization, whereas 52 patients had an infarction precipitating the unstable angina within the preceding 30 days (Group II). Emergent coronary artery bypass grafting was performed in all 100 patients irrespective of ventricular function, hemodynamic status, or coronary anatomy. Management protocols included prompt surgical intervention, preoperative stabilization with the balloon pump in LM or TVD, meticulous myocardial protection, and complete coronary revascularization. An average of 3.6 grafts were placed in each patient. There were two hospital deaths in Group I, and two in Group II. Two-year survival was 90% in Group I and 88% in Group II, and 81% of surviving patients were NYHA Class I or II. Thus, refractory UA denotes particularly severe coronary disease with a high incidence of LM, TVD, and depressed EF. Baseline clinical characteristics, criteria for operation, and expected results in the postinfarction group seem to be similar to the unstable angina group in general. Cardiac anatomic and functional variables no longer constitute operative contraindications. Aggressive operative management is safe, and the current risk may be less dependent on coronary anatomy and ventricular function than previously appreciated.

Adult↗

Equine colonic motility: interactions among wall motion, propulsion, and fluid flow.

Transmission of intestinal content with respect to wall position and intraluminal pressure was studied using implanted catheters in portions of the haustrated left ventral colon and nonhaustrated pelvic flexure and left dorsal colon in 3 conscious, standing, and feeding ponies. Wall position and content movement was studied in 1 noncatheterized conscious pony that was standing and eating. When coordinated wall movements involving greater than or equal to 30 cm of adjacent colon were seen, point-to-point content movement accompanied intraluminal pressure peaks occurring in the same direction. Near the pelvic flexure, intraluminal pressure peak maximums coincided and reduced colonic diameters and reduced intercatheter distances. Qualitative observation of 3 related aspects of intestinal motility: wall motion, propulsion, and fluid movement can be studied in the conscious feeding pony.

Animals↗

The natural history and recommended management of patients with traumatic coronary artery fistulas.

Traumatic coronary artery fistulas are reported less often than other complications resulting from both penetrating and blunt trauma to the heart. We describe a 50-year-old man in whom the natural history of a traumatic coronary fistula is well documented. This patient, who was referred for evaluation and treatment of complications of a traumatic coronary artery fistula resulting from a shrapnel injury 31 years before admission to the hospital, had five cardiac catheterizations prior to undergoing definitive surgical repair. During this period, he progressed from being totally asymptomatic to having disabling angina and congestive heart failure. These symptoms developed even though the patient's left-to-right shunt remained constant; moreover, the symptoms appeared to develop secondary to a "steal" of myocardial blood flow from the uninvolved coronary arterial bed through tortuous collaterals. Based on this experience and supported by published reports of 25 other patients, we recommend that nearly all patients with traumatic coronary artery fistulas be considered as candidates for elective surgical repair in order to prevent the eventual development of serious and possibly life-threatening complications. Operative repair can be accomplished safely with excellent long-term results.

Angina Pectoris↗

Evidence that ischemic cell death begins in the subendocardium independent of variations in collateral flow or wall tension.

Irreversible ischemic injury occurs after coronary artery occlusion in vivo, first in the subendocardium and progressing toward the subepicardium over time, presumably due to transmural variations in collateral flow or wall tension. In this study, 10 left ventricular globally ischemic slabs were created that were free of wall tension and collateral flow. The onset and completion of ischemic contracture were identified by means of a new tissue compressibility gauge designed for these studies. Transmural samples were obtained at 15 min intervals for determination of high-energy nucleotide levels and for ultrastructural analysis. The results show that there is a statistically significant gradient of ATP depletion, with the subendocardium consistently showing accelerated energy utilization compared with the subepicardium (p less than .05). Ultrastructural evidence of irreversible injury first appeared in the subendocardium at the onset of ischemic contracture and occurred when ATP levels declined to less than 1 mumol/g wet weight. In summary, these data show that during total ischemia in vitro, cell death begins in the subendocardium at the onset of ischemic contracture and progresses toward the subepicardium over time. These changes occurred independent of variations in collateral flow or wall tension. The results suggest that the increased risk of the subendocardium to ischemic injury previously noted in vivo may occur not only because of variations in collateral flow and wall tension, but may also be secondary to an increased metabolic rate of the subendocardium resulting in faster ATP use during the period of ischemia.

Adenosine Diphosphate↗