M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate.

The human protease plasmin plays a crucial role in the capacity of the group A streptococcus (GAS; Streptococcus pyogenes) to initiate invasive disease. The GAS strain NS88.2 was isolated from a case of bacteremia from the Northern Territory of Australia, a region with high rates of GAS invasive disease. Mutagenesis of the NS88.2 plasminogen binding M protein Prp was undertaken to examine the contribution of plasminogen binding and cell surface plasmin acquisition to virulence. The isogenic mutant NS88.2prp was engineered whereby four amino acid residues critical for plasminogen binding were converted to alanine codons in the GAS genome sequence. The mutated residues were reverse complemented to the wild-type sequence to construct GAS strain NS88.2prpRC. In comparison to NS88.2 and NS88.2prpRC, the NS88.2prp mutant exhibited significantly reduced ability to bind human plasminogen and accumulate cell surface plasmin activity during growth in human plasma. Utilizing a humanized plasminogen mouse model of invasive infection, we demonstrate that the capacity to bind plasminogen and accumulate surface plasmin activity plays an essential role in GAS virulence.

Endothelin B receptors are functionally important in mediating vasoconstriction in the systemic circulation in patients with left ventricular systolic dysfunction.

OBJECTIVES: This study was designed to assess the functional importance of endothelin (ET)B receptors in patients with left ventricular systolic dysfunction (LVSD) by comparing the hemodynamic effects of ET-1, a nonselective ET(A) and ET(B) agonist, with ET-3, a selective ET(B) receptor agonist. BACKGROUND: Knowledge of the functional importance of ET(B) receptors in mediating vasoconstriction in chronic heart failure will help determine whether antagonists at both ET(A) and ET(B) receptors are required to fully prevent vasoconstriction to endogenously produced ET-1. METHODS: We infused ET-1 (5 and 15 pmol/min) and ET-3 (5 and 15 pmol/min) into two separate groups of eight patients with LVSD with similar baseline hemodynamic indices. Hemodynamics were measured using a pulmonary thermodilution catheter and an arterial line. RESULTS: Endothelin-1 infusion led to systemic vasoconstriction, with a rise in mean arterial pressure (mean +/- SEM 100 +/- 3 to 105 +/- 3 mm Hg, p < 0.02) and systemic vascular resistance (1,727 +/- 142 to 2,055 +/- 164 dyn/s/cm(-5), p < 0.001) and a fall in cardiac index (2.44 +/- 0.21 to 2.22 +/- 0.20 liters/min/m , p < 0.01). Endothelin-3 infusion also led to systemic vasoconstriction, with a rise in mean arterial pressure (99 +/- 6 to 105 +/- 6 mm Hg, p < 0.01) and systemic vascular resistance (1,639 +/- 210 to 1,918 +/- 245 dyn/s/cm(-5), p < 0.01) and a fall in cardiac index (2.66 +/- 0.28 to 2.42 +/- 0.24 liters/min/m2, p < 0.05). Pulmonary hemodynamic measurements did not change significantly in either group. CONCLUSIONS: Both ET-1 and ET-3 infusions led to systemic vasoconstriction; the hemodynamic changes observed were of a similar magnitude at the same molar concentration. This suggests that ET(B) receptors are functionally important in mediating vasoconstriction, at least in the systemic circulation, in patients with LVSD.

Endothelin-1 has haemodynamic effects at pathophysiological concentrations in patients with left ventricular dysfunction.

OBJECTIVES: Plasma levels of immunoreactive endothelin-1 (ET-1) are raised in chronic heart failure. Whether plasma ET-1 contributes to the haemodynamic derangement found in chronic heart failure is not known. We investigated the effects of exogenous ET-1 on the pulmonary and systemic vasculature in patients with left ventricular systolic dysfunction (LVD), with or without overt heart failure. METHODS: ET-1 was infused at 1, 5 and 15 pmol/min into a distal pulmonary artery of ten patients with LVD to achieve plasma concentrations of ET-1 similar to those found in patients with heart failure and pulmonary hypertension. Haemodynamics were measured using a pulmonary thermodilution catheter and an arterial line. Intravascular Doppler and local pulmonary angiography were used to assess local pulmonary blood flow in the first four patients. RESULTS: Systemic haemodynamic changes occurred with ET-1 infusion: mean arterial pressure (100 +/- 3 [standard error of the mean]) to 107 +/- 3 mmHg; p < 0.01) and systemic vascular resistance (1699 +/- 118 to 2033 +/- 135 dynes s/cm5; p < 0.001) rose, while the cardiac index fell from 2.43 +/- 0.17 to 2.20 +/- 0.16 l/min/m2 (p < 0.002). Mean pulmonary artery pressure (21 +/- 2 mmHg) and pulmonary vascular resistance (151 +/- 14 to 147 +/- 14 dynes s/cm5) did not change however. CONCLUSIONS: Exogenous ET-1, when infused to achieve plasma concentrations similar to those in severe heart failure and pulmonary hypertension, causes systemic but not pulmonary vasoconstriction.

Coxsackie B virus infection in coronary care unit patients.

It has been suggested that Coxsackie B virus infections may play a part in causing or triggering myocardial infarction. This study was designed to compare the incidence of such infections in Coronary Care Unit patients and normal controls. The choice of a suitable criterion for diagnosis of Coxsackie infection is discussed fully. Two hundred and fifty admissions to a Coronary Care Unit and 100 control subjects had a serum sample tested by microneutralisation for Coxsackie B antibodies. The incidence of infection among 130 patients diagnosed as acute myocardial infarction was 5% compared with 4% in the control group. In a subgroup classified as non-transmural myocardial infarction, the incidence of infection was 14%. The sex ratio of this group differed from the myocardial infarction group as a whole suggesting that the non-transmural group may not have been homogeneous. Normal coronary arteriograms were subsequently found in three patients who were diagnosed as non-transmural myocardial infarction but who had serological evidence of recent Coxsackie infection. This study does not demonstrate an association between Coxsackie infection and myocardial infarction as a whole and does not support the view that Coxsackie infection causes or provokes myocardial infarction. It does, however, suggest that myocarditis may simulate non-transmural infarction.

Peripheral pulmonary artery aneurysm in a patient with limited respiratory reserve: controlled resection using cardiopulmonary bypass.

Pulmonary artery aneurysms are rare lesions for which operative management is not frequently undertaken. When operation is indicated, central lesions involving the pulmonary trunk, right main pulmonary artery, or left main pulmonary artery are repaired using cardiopulmonary bypass. Peripheral aneurysms in segmental intrapulmonary arteries have been managed most frequently by lobectomy, but occasionally by aneurysmectomy and pulmonary arterial repair. We used cardiopulmonary bypass for peripheral pulmonary aneurysmectomy in a patient with limited respiratory reserve because he had undergone prior contralateral bilobectomy; this allowed controlled resection while preserving a maximal amount of pulmonary parenchyma.

Electrical cardioversion for atrial fibrillation: outcomes in "real-life" clinical practice.

BACKGROUND: There is currently considerable debate with regard to the optimal management of atrial fibrillation/flutter (AF), including the long-term success of electrical cardioversion and the duration of anti-coagulation thereafter. The aim of this study was to investigate the current management and outcomes of electrical cardioversion in unselected patients in ordinary clinical practice. METHODS: A prospective, observational study of 111 consecutive patients with AF who had been referred for electrical cardioversion was undertaken in a large teaching hospital. After cardioversion, patients were followed-up for 12 months or until death if this occurred earlier. RESULTS: Sinus rhythm was restored immediately in 96 of 111 (86%) patients. Only 54 of 88 (61%) patients in sinus rhythm at discharge remained in this rhythm at 1 month. Of these 54, a further 21 (39%) had relapsed into AF by 12 months. Independent predictors of sinus rhythm at discharge were younger age (for a difference of 5 years, odds ratio=1.54; 95% confidence interval 1.04 to 1.16; P=0.002) and absence of hypertension (1.73, 1.22-1.91; P=0.015). The presence of sinus rhythm at discharge (6.4, 1.6-25.3; P=0.007) was an independent predictor of sinus rhythm at 1 month, whereas older age was a negative predictor (0.96, 0.92-1.0; P=0.05). Health-related quality of life improved at 1 and 12 months in those patients who remained in sinus rhythm compared to those who remained in AF. CONCLUSIONS: Though electrical cardioversion for AF has a high initial success rate only a minority of patients remained in sinus rhythm 1 year. The common practice of discontinuing anticoagulant treatment in patients in sinus rhythm at 1 month may be unsafe. Long-term maintenance of sinus rhythm is, however, associated with better health-related quality of life.

Factors affecting patient radiation exposure during routine coronary angiography in a tertiary referral centre.

Cardiac catheterization is carried out by an increasing number of operators from district hospitals as well as tertiary referral centres. Procedures are not standardized and are at the discretion of individual operators. The purpose of this study was to describe the pattern of patient radiation dose and screening times associated with diagnostic cardiac catheterization, and explore determinants of radiation dose to patients and staff. Data were collected from 1337 diagnostic procedures carried out in two cardiac catheterization laboratories from January to June 1998. Screening time and radiation dose measured by dose-area product (DAP) meter were recorded. Status of the operator and type of investigation were determined. 22 operators had performed at least 15 left ventriculograms with coronary angiography (total 944 procedures). The average (+/- SD) was 40 (+/- 22) per operator. Screening times for individual operators varied from 2.0 (+/- 1.3) min to 5.0 (+/- 4.3) min with no relationship between time and number of cases. Consultants and visiting physicians had longer screening times and greater patient DAP readings. In comparison with 115 cases of coronary angiography alone, left ventriculography increased DAP reading from 14.24 (+/- 11.7) Gy cm2 to 20.26 (+/- 0.47) Gy cm2 (p < 0.0001). In 106 cases of coronary artery bypass graft angiography, an aortogram (n = 53) did not add significantly to radiation dose or screening time. A right heart catheter added approximately 5 min to screening time (9.13 (+/- 0.63) min with right heart (n = 83) vs 3.96 (+/- 0.12) min without right heart (n = 1234)), but did not affect radiation dose significantly. There is a wide range of screening times and radiation doses related to diagnostic cardiac catheterization. Visiting and consultant staff use greater radiation doses. Left ventriculography adds significantly to patients' radiation exposure. Aortography does not add significantly to radiation dose in cases of graft angiography.

Hemopericardium and tamponade following intracoronary thrombolysis with streptokinase.

Two patients underwent surgery for hemopericardium and pericardial tamponade after intracoronary thrombolysis by streptokinase for acute myocardial infarction. In both instances, the artery had reopened, but left ventricular function had not improved. A subxiphoid pericardial window relieved the tamponade, and both patients made good recovery. Hemopericardium is rare in myocardial infarction without cardiac rupture or anticoagulant therapy, and may constitute a specific complication of reperfusion with streptokinase. Pericardial window may be preferable to pericardiocentesis because of the possibility of cardiac rupture.

The effects of exercise in a coronary rehabilitation programme.

Twenty-two male and female patients who had recently suffered a myocardial infarction were randomly assigned to a treatment group who participated in a 10-week exercise-based cardiac rehabilitation programme or a routine care group who did not participate in the rehabilitation programme. Physiological and psychological function were assessed before the programme started and after it finished. Results indicated that the treatment group did not improve physiological functioning more than the control group but they did evidence statistically significant improved psychological functioning. This investigation appears to be the first attempt to assess the potential benefits of an exercise-based cardiac rehabilitation programme in Glasgow and supports the suggestion that exercise-based cardiac rehabilitation has psychological benefits.