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Biomedical subjects

J E Lowe

Publications and source records attributed to J E Lowe.

231 records · Page 13Linked to original sources

Ultrastructure of electrophysiologically identified human sinoatrial nodes.

The ultrastructure of freshly excised human sinus node tissue was studied. In three female patients (ages 20, 30, and 36 years) medically refractory disabling episodes of inappropriate sinus tachycardia were surgically treated by extirpation of the sinus node. Each patient underwent intraoperative electrophysiological mapping to determine the area of earliest atrial activation. This area corresponded anatomically to the region of the sinoatrial node and was excised in each patient, the defect repaired using a pericardial patch. The freshly excised SA nodes underwent ultrastructural study. Three types of myocardial cells were identified: pacemaker or polygonal cells with clear cytoplasm, few mitochondria and sparse numbers of contractile elements (P cells); a transitional cell with slightly increased numbers of myofibrils (T cells); and typical atrial myocardial cells with normal numbers of contractile elements. These cell types have previously been identified in post-mortem studies of presumed SA node. The current study confirms the cell types in electrophysiologically documented SA nodes. The one abnormal finding observed in transitional cells in all patients was an increased number of lipofuscin-laden vacuoles. These vacuoles are considered a sign of cell degeneration and their occurrence was totally unexpected in these young adults. In summary, ultrastructural study of electrophysiologically documented human SA nodes confirmed the cell types identified in post-mortem studies. Furthermore, lipofuscin-laden vacuoles were increased in these three patients and this finding may serve as an ultrastructural marker associated with the syndrome of inappropriate sinus tachycardia.

Adult↗

Comparison of direct mechanical ventricular actuation and cardiopulmonary bypass.

Direct mechanical ventricular actuation (DMVA) is a non-blood-contacting method for biventricular support. To compare effects of DMVA and cardiopulmonary bypass (CPB), 13 swine were supported by DMVA or CPB during 4 hours of ventricular fibrillation. Hearts were then rapidly excised and sectioned into right ventricular (RV) and left ventricular (LV) free wall slabs and subjected to total normothermic ischemia. Time to peak ischemic contracture (TIC) of LV endocardium (endo), LV epicardium (epi) and RV were determined using Millar needle transducers. Mean TIC was compared between DMVA (n = 6), CPB (n = 7), and control (n = 18). Significant decreases in LV endo TIC were found after DMVA (53.3 +/- 3.3 min) and CPB (56.2 +/- 2.4 min) compared with control (62.5 +/- 1.0), p less than 0.05. Myocardial blood flow was measured using microspheres during normal sinus rhythm and after 2 and 4 hr of circulatory support. Nonsignificant decreases in endo flow occurred during CPB and DMVA compared with control. LV endo adenosine triphosphate (ATP) levels (mumol/g dry weight) were significantly decreased after DMVA (9.0 +/- 2.5) and CPB (4.0 +/- 2.7) compared with control (17.8 +/- 0.6), p less than 0.05. Although CPB maintained mean arterial pressure by increased pump flows (mean, 129 ml/kg/min) and LV intracavitary pressures were kept below 5 mmHg with LV venting, resulting endo flows and ATP levels were decreased. DMVA generated decreased cardiac outputs (mean, 67 ml/kg/min) under these vasodilated states, yet maintained endo flow and ATP levels as well as CPB. These experimental data show that different mechanisms of myocardial perfusion and metabolism result from CPB and DMVA.

Animals↗

Cardiac pathology following resuscitative circulatory support. Direct mechanical ventricular actuation versus cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is currently advocated for treating refractory cardiac arrest. Direct Mechanical Ventricular Actuation (DMVA) is an alternative method that does not contact the blood and has other unique advantages for providing resuscitative circulatory support, including rapid application and relative technical simplicity. The purpose of this study was to assess pathologic changes in the heart following resuscitation with either CPB or DMVA. Dogs (n = 22) received 1 hr of CPB (n = 11) or DMVA (n = 11) following a 12.5 min cardiac arrest. All deaths [4/11 (CPB) vs. 2/11 (DMVA), p = 0.31] occurred during the initial 24 postoperative hours. At 7 days, survivors had magnetic resonance imaging to determine cardiac ejection fraction [46% (CPB) vs. 51% (DMVA), p = 0.39], as well as the presence of cardiac wall motion abnormalities [50% (CPB) vs. 33% (DMVA), p = 0.57] and gross cardiac lesions [17% (CPB) vs. 17% (DMVA)]. The survivor's hearts were then extirpated, fixed, and examined for gross lesions [2/7 (CPB) vs. 0/9 (DMVA), p = 0.17]. Transmural sections of the anterior and posterior papillary muscles were histologically evaluated. The severity and extent of epicardial fibrosis and focal myocyte necrosis did not differ between groups. These data demonstrate that DMVA does not cause more myocardial trauma than CPB when used to provide resuscitative circulatory support. Therefore, the unique attributes of DMVA may improve resuscitation outcome in patients who suffer refractory cardiac arrest, without additional risk of cardiac injury.

Animals↗

Intraoperative timing may provide criteria for use of post-cardiotomy ventricular assist devices.

When surgeons consider ventricular assist devices (VADs) for post-cardiotomy support, unnecessary delays and early use can have detrimental effects on patient outcome. The authors analyzed the timing of intraoperative events in all patients receiving post-cardiotomy VAD support at their institution during a 2-1/2 year period (N = 17). They used ability to wean patients from VAD support as a measure of outcome. Neither preoperative risk factors nor the timing of distinct intraoperative events (e.g., cross-clamp time, total bypass time, delay to VAD) significantly differed between those patients able (Group I, n = 9) and those unable (Group II, n = 8) to be weaned from VAD support. The authors did find, however, that the time intervals from completion of the cardiac procedure to insertion of either an intra-aortic balloon pump (time to IABP) or VAD (time to VAD) were predictive of outcome when normalized to the duration of the cardiac procedure (DCP). [Time to IABP]/DCP ratios of < 1.0 versus > 1.0 (p = 0.02) and [time to VAD]/DCP ratios of < 2.5 versus > 2.5 (p = 0.10) each segregated Group I and II patients, respectively. Appropriate timing criteria for VAD insertion may be predicted during surgery by consideration of the duration of the cardiac procedure. This approach may attenuate tendencies to delay VAD use without leading to premature VAD insertion in the post-cardiotomy setting.

Aged↗

Prophylactic implantable defibrillator patches in patients at high risk for malignant ventricular dysrhythmias.

The indications for prophylactically placing implantable cardioverter defibrillator (ICD) patches at cardiac surgery are unclear. Over the past 4 years, 25 patients have undergone placement of prophylactic ICD patches at the authors' institution. Indications were severe coronary artery disease with ventricular tachycardia (VT) (n = 14) or ventricular fibrillation (VF) (n = 2), and left ventricular aneurysmectomy and/or subendocardial resection (SER) (n = 9). Four patients died in-hospital, three from refractory VT (which could be transthoracically cardioverted until recurrence was unremitting), and one from congestive heart failure (CHF). All of the remaining 21 patients underwent post-operative electrophysiologic studies (EPS), and 12 had inducible VT (8/14 CABG, 4/7 SER). Eight of the 12 inducible patients had generators implanted, whereas 3 patients were controlled medically. One patient refused generator implantation and died at home from sudden cardiac death, and one initially non-inducible patient required late ICD generator placement, yielding a total of nine patients who received generators. All nine of these patients are currently alive at 14 +/- 7 months follow-up, and five have subsequently received appropriate ICD discharges. In patients undergoing cardiac surgery considered preoperatively or intraoperatively to be at increased risk for VT/VF and too unstable for preoperative EPS, prophylactic ICD patches should be considered.

Aged↗

Myocardial tolerance to mechanical actuation is affected by biomaterial characteristics.

Direct mechanical ventricular actuation (DMVA) uses a pressure regulated heart cup, fabricated from silicone rubber (SR) for mechanical massage of the heart. Because DMVA has demonstrated potential for long-term circulatory support, investigations are currently exploring the use of more durable materials for fabricating DMVA heart cups. This study assessed the acute effects of heart cups fabricated from SR versus polyurethane (PU) on the myocardium. Dogs (n - 18) received DMVA for 4 hr of ventricular fibrillation (VF) using either SR (n = 10) or PU (n = 8) cups. Microspheres were used to determine perfusion during sinus rhythm (control) and at 2 and 4 hr of support. After support, myocardial biopsies were assayed for high energy phosphate content. Results demonstrated that PU cups required relatively frequent adjustments in drive line parameters that were likely due to material softening during PU cup support. Both PU and SR cups achieved similar hemodynamics during 4 hr of support. Myocardial perfusion, however, demonstrated a marked hyperemia at 4 hr of PU versus SR cup support. Regional high energy phosphate content was significantly decreased in hearts supported by PU versus SR cups. These results suggest that the relatively compliant characteristics of SR materials are important for achieving effective DMVA support without injuring the myocardium.

Adenosine Triphosphate↗

Prolonged total circulatory support using direct mechanical ventricular actuation.

Direct mechanical ventricular actuation (DMVA) is a unique, non blood contacting method for biventricular cardiac assist. Although DMVA has successfully provided cardiac assist for more than 7 days in humans, with long-term survival, its potential for long-term circulatory support has not been adequately investigated. DMVA has not been studied in the large ruminants commonly used to evaluate support devices. To develop a large animal experimental model of prolonged total circulatory support using DMVA, Suffolk sheep (n = 10) underwent sterile instrumentation for hemodynamic and chemistry monitoring. After baseline values were obtained, a left lateral thoracotomy and pericardotomy were performed. Upon electrical ventricular fibrillation (VF), DMVA was begun and the thoracotomy closed. Total circulatory support was continued until mean arterial pressure (MAP) persisted below 50% of the baseline value for more than 1 hr, with a goal of 7 days' support. Mean duration (plus or minus the standard deviation [SD]) of circulatory support was 65.9 +/- 56.8 hr (range, 10-168 hr). Pressors were not used during DMVA support. The subject supported for the maximal time (7 days) was defibrillated into sinus rhythm. No CK-MB fraction was greater than 1%, suggesting that DMVA, even with prolonged application during VF, does not result in myocardial injury. Blood urea nitrogen and creatinine levels indicate renal function was preserved. The model described represents the longest period any animal has been supported in VF using DMVA. This new model will be useful in determining what limitations, if any, exist to the prolonged use of DMVA for circulatory support.

Animals↗

CT demonstration of myocardial perforation by a pacemaker lead.

We report a case of perforation of the right atrium by a transvenous right atrial appendage pacemaker lead diagnosed by CT. Routine radiologic assessment was unable to demonstrate the perforation. Computed tomography is recommended in cases where pacemaker perforation is clinically suspected but not confirmed by conventional radiographic means.

Aged↗

Improved donor myocardial recovery with a new lazaroid lipid antiperoxidant in the isolated canine heart.

U74006F is a new 21-amino steroid (lazaroid) that prevents lipid peroxidation without glucocorticoid or mineralocorticoid side effects. Reperfusion injury has been reduced by the addition of various free radical scavengers and antiperoxidants to the reperfusate. To assess the effect of U74006F on reperfusion of donor hearts subjected to prolonged hypothermic ischemia, 21 isolated canine hearts were divided into three groups: control (group 1), drug (2 mg/kg) injected into the oxygenated blood perfusate immediately before 4 hours of preservation (group 2), and drug (2 mg/kg) injected 1 hour before heart isolation and again 15 minutes before reperfusion (group 3). After control left ventricular function studies (with an intraventricular balloon) and biopsy for high-energy phosphates and dry/wet ratios, the hearts were arrested with cold cardioplegia and cooled for 4 hours then reperfused for 3 hours. Left ventricular work was calculated by systolic and diastolic pressure curves, which showed a better return of function in group 3 hearts (1625, 2150, and 3493 mm Hg/ml in groups 1, 2, and 3, respectively, at 180 minutes of reperfusion; p = 0.02). This was likely the result of improved diastolic compliance in group 3. Dry/wet ratios showed increased tissue edema in all hearts at the end of reperfusion. Although high-energy phosphate concentrations were not different between groups, adenosine was best preserved in group 3 (p = 0.03), suggesting reduced washout of this precursor. In conclusion, administration of U74006F before preservation and reperfusion may be useful for donor heart protection.

Adenine Nucleotides↗

Myocardial tolerance to ischemia after resuscitation. Direct mechanical ventricular actuation versus cardiopulmonary bypass.

This study assessed myocardial ischemia after resuscitation from cardiac arrest using direct mechanical ventricular actuation (DMVA) or cardiopulmonary bypass (CPB). Myocardial ischemic tolerance was better after DMVA resuscitation. Resuscitation using DMVA, when compared with CPB, may improve outcome when subsequent coronary artery bypass grafting (CABG) is required.

Animals↗

Effect of lung inhomogeneity on partial flow-volume manoeuvres.

We evaluated the effects of inhomogeneous lung emptying on the relationship of partial to maximal complete expiratory flow by obtaining pre- and post-metaproterenol maximal (MEFV) and partial flow-volume curves in normal subjects and asthmatics. Partial curves were initiated between 65-70% of vital capacity after inspiration from functional residual capacity (PEFV curve) or after deflation from total lung capacity (PEFVDI curve). Since PEFVDI curves were initiated at lower lung volumes than MEFV manoeuvres (but with a similar volume history), non-homogeneous emptying should cause higher flow on PEFVDI than on MEFV manoeuvres. Expiratory flow (Vmax) was highest on MEFV manoeuvres in normals and PEFV curves in asthmatics. Pre- and post-metaproterenol Vmax was very similar on MEFV and PEFVDI manoeuvres in both groups, although Vmax(MEFV) slightly but significantly exceeded Vmax(PEFVDI) in normals and the reverse was true in asthmatics. Lung elastic recoil did not differ significantly on MEFV and PEFVDI manoeuvres in either group. We conclude that asthmatics demonstrate inhomogeneous emptying. However, because flow-volume curves are relatively insensitive to sequences of lung emptying, inhomogeneous emptying during forced expiration only has minor effects on the relationship of partial to maximal expiratory flow.

Adult↗

Sensing lead insulation fractures following implantable cardioverter-defibrillator placement.

The insulation of implantable cardioverter-defibrillator (ICD) sensing leads can fracture, causing device malfunction. Before March 1989, 32 patients received silicon CPI K54 sensing leads. Of these, four (12.5%) experienced discharges while in sinus rhythm. Subsequent ICD interrogation revealed that abdominal muscular contraction triggered discharges in two patients, but no abnormal sensing could be elicited in the other two patients. These patients subsequently were found to have sensing lead fractures. All sensing leads appeared intact radiographically but at reoperation were found to have insulation fractures 2-4 cm from the pin. The mechanism of fracture appears to be related to chronic intermittent lead compression between the anterior abdominal wall musculature and the ICD generator. Since March 1989, 134 patients have undergone ICD implantation with improved CPI 4312 sensing leads; none of these patients has experienced sensing lead fractures. The insulation of these leads is 2.5 times thicker than the K54 (1.0 mm vs. 0.4 mm). Patients with K54 sensing leads are at an increased risk for sensing lead insulation fracture and merit close surveillance. More importantly, sensing lead fractures must be considered in patients who present with inappropriate ICD discharges.

Defibrillators, Implantable↗