Haemodynamic effects of frusemide and its influence on repetitive rapid volume loading in acute myocardial infarction

The haemodynamic effects of intravenous frusemide (1 mg/kg)were studied in 22 male patients with left ventricular failurefollowing acute myocardial infarction. Radiographic pulmonaryoedema was present in all patients and their average left heartfilling pressure was 20 mmHg. Bolus injection of the drug wasfollowed by immediate increases in systemic arterial pressure(P < 0.05) and heart rate (<0.05); these declined to pre-injectionvalues after 60 min. Following frusemide there were progressivereductions in left heart filling pressure (P < 0.01), thermodilutioncardiac output (P < 0.01) and stroke volume (P < 0.05)and a progressive increase in the derived systemic vascularresistance (P < 0.05). There was an average diuresis of 860ml during the 90 min following the frusemide injection. Theinfluence of frusemide on left ventricular performance was studiedby comparing the circulatory effects of passive leg raisingin the control period with those at 30, 60 and 90 min afterthe drug. In the control period this manoeuvre increased leftheart filling pressure, but not heart rate, cardiac output,stroke volume or systemic vascular resistance. Ninety minutesafter frusemide, but not before, passive leg raising resultedin a significant increase in cardiac output (P < 0.01) andstroke volume at a similar increment in filling pressure anda significant reduction in the systemic vascular resistance(P <0.05). These circulatory actions of intravenous frusemideare compatible with initial arteriolar constriction and venodilatationfollowed by depletion of blood volume with subsequent changein left ventricular pumping performance.     

The Renin–Angiotensin System Mediates the Effects of Stretch on Conduction Velocity,Connexin43 Expression,and Redistribution in Intact Ventricle

Effect of Stretch on Conduction and Cx43 . Introduction: In disease states such as heart failure, myocardial infarction, and hypertrophy, changes in the expression and location of Connexin43 (Cx43) occur (Cx43 remodeling), and may predispose to arrhythmias. Stretch may be an important stimulus to Cx43 remodeling; however, it has only been investigated in neonatal cell cultures, which have different physiological properties than adult myocytes. We hypothesized that localized stretch in vivo causes Cx43 remodeling, with associated changes in conduction, mediated by the renin–angiotensin system (RAS). Methods and Results: In an open‐chest canine model, a device was used to stretch part of the right ventricle (RV) by 22% for 6 hours. Activation mapping using a 312‐electrode array was performed before and after stretch. Regional stretch did not change longitudinal conduction velocity (post‐stretch vs baseline: 51.5 ± 5.2 vs 55.3 ± 8.1 cm/s, P = 0.24, n = 11), but significantly reduced transverse conduction velocity (28.7 ± 2.5 vs 35.4 ± 5.4 cm/s, P < 0.01). It also reduced total Cx43 expression, by Western blotting, compared with nonstretched RV of the same animal (86.1 ± 32.2 vs 100 ± 19.4%, P < 0.02, n = 11). Cx43 labeling redistributed to the lateral cell borders. Stretch caused a small but significant increase in the proportion of the dephosphorylated form of Cx43 (stretch 9.95 ± 1.4% vs control 8.74 ± 1.2%, P < 0.05). Olmesartan, an angiotensin II blocker, prevented the stretch‐induced changes in Cx43 levels, localization, and conduction. Conclusion: Myocardial stretch in vivo has opposite effects to that in neonatal myocytes in vitro. Stretch in vivo causes conduction changes associated with Cx43 remodeling that are likely caused by local stretch‐induced activation of the RAS. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1276‐1283, November 2010)     

Long-term follow-up of children inserted with T-tubes as a primary procedure for otitis media with effusion

This study reviews 90 children who underwent T-tube insertion as a primary procedure for otitis media with effusion over a 3-year period and compares the long-term results with a similar group, matched in terms of age, treated with conventional Shepard gromments during the same period. Fifty-one patients (102 ears) in the T-tube group and 53 patients (106 ears) in the Shepherd grommet group attended for clinical review, a minimum of 6 years post-surgery. No significant difference was found between the two groups in terms of pre-operative symptoms (P= 0.95). operative findings (P= 0.84), hearing loss (P= 0.75), or degree of retraction or tympanosclerosis of the tympanic membrane (P= 0.80). A perforation rate of 24% in the T-tube group, compared with 2% in the Shepard grommet group (P= 0.001) is directly attributable to T-tube insertion. Furthermore, the risk of perforation was related to the duration of the ventilation tube in the typanic membrane.     

The association of hepatitis C viral infection with porphyria cutanea tarda in the Lothian region of Scotland

Porphyria cutanea tarda (PCT) is believed to be associated with reduced hepatic uroporphyrinogen decarhoxylase activity and risk factors such as alcohol abuse and medication with oral contraceptives and certain other drugs. Recently it has been suggested that hepatitis C virus (HCV) infection may also he associated with PCT. We have therefore reviewed the prevalence of HCV infection in a series of patients with PCT in the Lothian region of Scotland. We identified 12 patients with PCT, all of whom had abnormal liver function tests. Liver histology revealed chronic active hepatitis in six patients, micronodular cirrhosis in lour patients, hepatocellular carcinoma in one patient and normal findings in one HIV positive patient. Out of 12 patients tested, 11 were positive for anti-HCV antibodies by second generation enzyme linked immunosorbent assay (ELISA 2), and by recombinant immunoblot assay (RIBA 2); positive serology was confirmed by polymerase chain reaction (PCR). In a second group of 14 patients with chronic HCV infection matched for age and sex with the PCT patients, all had normal urinary uroporphyrin excretion. We have thus confirmed in Scotland early reports from Spain and Italy that PCT is strongly associated with HCV infection. This could explain the development of inflammatory changes in the liver and progression of liver disease in patients with PCT. Porphyrin metabolism, however, appears normal in patients with chronic HCV infection without PCT.     

Lead-Induced Tricuspid Stenosis—Successful Management by Balloon Angioplasty

We describe a case of tricuspid stenosis in a young woman 11 years after endocardial ventricular lead implantation. The cause of the stenosis appears to have been perforation of the septal leaflet by the lead at the time of insertion. We further describe successful management with percutaneous balloon valvuloplasty without the need for lead removal.     

The effect on left ventricular performance of nifedipine and metoprolol singly and together in exercise-induced angina pectoris

Clinical concern still exists regarding the potentially deleteriousresults of the combined negative inotropic effects of cardiacbeta-adrenoceptor and slow calcium channel blockade in patientswith impaired left ventricular function due to coronary heartdisease. The haemodynamic effects of sublingual nifedipine (20mg) and intravenous metoprolol (10 mg) singly and in combinationwere therefore studied in 20 patients with severe angina pectorisassociated with angiographically documented coronary arterydisease. The plasma concentrations of each drug at the timeof the haemodynamic measurements were within the range associatedwith relief of exercise-induced anginal pain. Sitting at rest,nifedipine was associated with reductions in systemic arterialpressure (P < 0-05), systemic vascular resistance (P <0001), and increases in heart rate (P<0-01) and cardiac output(V<005) without significant change in the left heart fillingpressure. In contrast, sitting at rest, metoprolol was associatedwith reductions in systemic blood pressure (P < 0-05), heartrate (P<0-001) and cardiac output (P<005) and an increasein left heart filling pressure (P<0-01). After both drugs,similar directional changes were observed during upright bicycleexercise compared to the control exercise measurements. In combination,the negative inotropic effects of metoprolol were largely offsetby the reduction of the systemic vascular resistance due tonifedipine. Conversely the reflex tachycardia following nifedipinewas countered by metoprolol. Thus the combination reduced twoof the major determinants of left ventricular oxygen consumption,namely heart rate and systemic blood pressure, at the expenseof a small increase in left heart filling pressure. This mayhave explained the subjective improvement in anginal symptomsnoticed by the majority of the patients. The combination ofnifedipine andmetoprolol was haemodynamically more advantageousboth at rest and during exercise than either drug alone in ourpatients with depressed left ventricular function due to thecoronary heart disease.