Effects of a new cardiomyoplasty technique on cardiac function

OBJECTIVE: The current cardiomyoplasty technique was modified to maintain the resting tension of the latissimus dorsi muscle and to prevent lateral movement of the heart during muscle stimulation. The aim of this study is to compare the short term hemodynamic effects of the new cardiomyoplasty wrap (W1) with those of the clinically applied cardiomyoplasty wrap (W2). Preliminary indications of the long-term hemodynamic effects of W1 are presented. METHODS: In three acute experiments in sheep mean central venous pressure (MCVP), mean arterial pressure (MAP), mean cardiac output (MCOP), mean left ventricular systolic pressure (MLVSP), and mean left ventricular diastolic pressure (MLVDP) were measured for 30s before and five minutes after applying each procedure with and without stimulation of the muscle graft. The same parameters were also recorded 5min after removing each muscle wrap. Hemodynamic changes associated with unstimulated muscle wraps were compared to the baseline data. Hemodynamic effects of muscle stimulation were determined by comparing the assisted to the preceding unassisted cardiac cycle. The long-term effects of W1 on the hemodynamics of another three sheep were studied at 6-12months after the operation. The viability of the muscles used in the chronic experiments were evaluated by morphometric analysis. RESULTS: Unstimulated W2 significantly increased mean central venous pressure and reduced mean cardiac output. It also increased mean left ventricular diastolic pressure and reduced peak negative dP/dt. Unstimulated W1 had no deleterious effect on mean central venous pressure, mean left ventricular diastolic pressure or peak -dP/dt, but it also reduced mean cardiac output and increased mean left atrial pressure (MLAP). Synchronised muscle stimulation, in both techniques, augmented the mean arterial pressure, mean cardiac output and mean left ventricular systolic pressure. In W2, however, myostimulation was also associated with a significant increase of the mean left ventricular diastolic pressure. In two long-term experiments significant hemodynamic assistance was observed at 6months and at 1yr after W1. In those sheep 68% of the cross-sectional area of the muscle was well preserved. CONCLUSIONS: Unstimulated cardiomyoplasty wraps acutely impair left ventricular function in sheep. The new technique, however, may offer significant long-term hemodynamic assistance and adequate preservation of the structural and functional integrity of the muscle flap for up to 1yr.     

Acute coronary occlusion during percutaneous transluminal coronary angioplasty

Two hundred and forty percutaneous transluminal coronary angioplasty procedures were performed in three centres over a two year period. Acute occlusion of the vessel undergoing angioplasty was seen on 20 (8%) occasions. The cause of occlusion was determined angiographically and in some cases confirmed at the time of emergency open heart surgery. The mechanism of coronary occlusion was arterial dissection in six cases, persisting coronary arterial spasm in seven, and coronary thrombosis in four. In three patients the mechanism could not be determined. Immediate reintroduction of a balloon dilatation catheter was attempted in 10 patients and resulted in restoration of adequate coronary flow in six. The remaining 14 patients underwent open heart surgery as an emergency procedure.     

Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachycardia.

The effect of amiodarone on survival was assessed in patients with hypertrophic cardiomyopathy and ventricular tachycardia in a drug trial with historical controls. During 1976 and 1977, 24 hour (seven) or 48 hour (79) electrocardiographic monitoring was performed in 86 consecutive patients; 24 had ventricular tachycardia and received conventional antiarrhythmic agents. Nineteen clinical, echocardiographic, and haemodynamic features were assessed. Seven patients died suddenly during follow up of three years; of these, five had continued to have ventricular tachycardia and two had no documented ventricular tachycardia. During 1978 and 1979, ventricular tachycardia was detected during 48 hour electrocardiographic monitoring in 21 of the next 82 consecutive patients with hypertrophic cardiomyopathy. They received amiodarone (150-400 mg/day, median 300); ventricular tachycardia was suppressed in all during repeat 48 hour electrocardiographic examination. Two patients died suddenly during a three year follow up, but neither belonged to the amiodarone treated group with ventricular tachycardia. The clinical and haemodynamic variables were similar in patients taking amiodarone and conventional agents. The fact that control of ventricular arrhythmia with amiodarone is significantly associated with improved survival suggests that amiodarone may prevent sudden death in patients with hypertrophic cardiomyopathy and ventricular tachycardia.     

A new finite element approach for near real‐time simulation of light propagation in locally advanced head and neck tumors

Background and Objectives

Several clinical studies suggest that interstitial photodynamic therapy (I‐PDT) may benefit patients with locally advanced head and neck cancer (LAHNC). For I‐PDT, the therapeutic light is delivered through optical fibers inserted into the target tumor. The complex anatomy of the head and neck requires careful planning of fiber insertions. Often the fibers' location and tumor optical properties may vary from the original plan therefore pretreatment planning needs near real‐time updating to account for any changes. The purpose of this work was to develop a finite element analysis (FEA) approach for near real‐time simulation of light propagation in LAHNC.

Methods

Our previously developed FEA for modeling light propagation in skin tissue was modified to simulate light propagation from interstitial optical fibers. The modified model was validated by comparing the calculations with measurements in a phantom mimicking tumor optical properties. We investigated the impact of mesh element size and growth rate on the computation time, and defined optimal settings for the FEA. We demonstrated how the optimized FEA can be used for simulating light propagation in two cases of LAHNC amenable to I‐PDT, as proof‐of‐concept.

Results

The modified FEA was in agreement with the measurements (P = 0.0271). The optimal maximum mesh size and growth rate were 0.005–0.02 m and 2–2.5 m/m, respectively. Using these settings the computation time for simulating light propagation in LAHNC was reduced from 25.9 to 3.7 minutes in one case, and 10.1 to 4 minutes in another case. There were minor differences (1.62%, 1.13%) between the radiant exposures calculated with either mesh in both cases.

Conclusions

Our FEA approach can be used to model light propagation from diffused optical fibers in complex heterogeneous geometries representing LAHNC. There is a range of maximum element size (MES) and maximum element growth rate (MEGR) that can be used to minimize the computation time of the FEA to 4 minutes. Lasers Surg. Med. 47:60–67, 2015. © 2015 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.     

Investigation of a hemodynamic basis for syncope in hypertrophic cardiomyopathy. Use of a head-up tilt test.

BACKGROUND. Syncope and sudden death in hypertrophic cardiomyopathy may have a hemodynamic basis. The presence of a small ventricular cavity with high intracavity pressures may activate left ventricular baroreceptors and cause reflex hypotension as described in other populations with syncope. METHODS AND RESULTS. To investigate this potential mechanism of syncope in hypertrophic cardiomyopathy, we studied 17 patients with a history of syncope (syncopal), 19 without syncope (nonsyncopal), and nine normal control subjects by using a head-up tilt test. Head-up tilt at 60 degrees for 45 minutes was followed by 10-minute tilts during incremental doses of isoprenaline. Heart rate, blood pressure, and two-dimensional and Doppler echocardiography were monitored throughout. On tilting, hypertrophic cardiomyopathy patients showed a decline in mean arterial pressure of -5 +/- 6 mm Hg (p less than 0.001) compared with no change in control subjects (0.2 +/- 6 mm Hg, p = 0.9). Left ventricular outflow tract velocity decreased on tilting in control subjects (-8 +/- 6 cm/sec, p = 0.004) but increased in the syncopal and nonsyncopal patients (20 +/- 50 cm/sec, p = 0.05). Reflex hypotension with or without bradycardia, associated with syncope or presyncope, was induced in seven syncopal patients, two nonsyncopal patients, and two control subjects (p = 0.05). The early response to tilt in these subjects was characterized by maintenance of blood pressure but a greater increase in left ventricular fractional shortening than in the other subjects (10 +/- 8% versus 1 +/- 1%, p = 0.002). The onset of hypotension was associated with a trend toward further decreases in left ventricular diameters, outflow tract velocity, and transmitral flow velocities. In the remaining patients who had a negative test, transient hypotension (systolic pressure less than 100 mm Hg) occurred in seven syncopal patients and three nonsyncopal patients compared with none of the control subjects (p = 0.01). In total, hypotension was demonstrated in 82% of syncopal patients compared with 26% of nonsyncopal patients and 22% of control subjects (p = 0.001). CONCLUSIONS. Patients with hypertrophic cardiomyopathy and a history of syncope frequently display hypotension during head-up tilt. In some cases, sudden hypotension occurs and is usually associated with bradycardia and a reduced cavity size, findings compatible with activation of a ventricular baroreflex. In other cases, transient hypotension occurs and could be explained by an impairment of baroreceptor function. These mechanisms may contribute to the occurrence of syncope in daily life.     

Specific deletion of NaV1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndrome

Heterozygous loss-of-function mutations in the brain sodium channel Na(V)1.1 cause Dravet syndrome (DS), a pharmacoresistant infantile-onset epilepsy syndrome with comorbidities of cognitive impairment and premature death. Previous studies using a mouse model of DS revealed reduced sodium currents and impaired excitability in GABAergic interneurons in the hippocampus, leading to the hypothesis that impaired excitability of GABAergic inhibitory neurons is the cause of epilepsy and premature death in DS. However, other classes of GABAergic interneurons are less impaired, so the direct cause of hyperexcitability, epilepsy, and premature death has remained unresolved. We generated a floxed Scn1a mouse line and used the Cre-Lox method driven by an enhancer from the Dlx1,2 locus for conditional deletion of Scn1a in forebrain GABAergic neurons. Immunocytochemical studies demonstrated selective loss of Na(V)1.1 channels in GABAergic interneurons in cerebral cortex and hippocampus. Mice with this deletion died prematurely following generalized tonic-clonic seizures, and they were equally susceptible to thermal induction of seizures as mice with global deletion of Scn1a. Evidently, loss of Na(V)1.1 channels in forebrain GABAergic neurons is both necessary and sufficient to cause epilepsy and premature death in DS.