Angiotensin-converting enzyme inhibition enhances a subthreshold stimulus to elicit delayed preconditioning in pig myocardium.

OBJECTIVES: We assessed the effect of angiotensin-converting enzyme (ACE) inhibition in combination with a subthreshold preconditioning (PC) stimulus to elicit delayed preconditioning against infarction in pig myocardium. BACKGROUND: Bradykinin triggers early PC. Angiotensin-converting enzyme inhibitors increase local bradykinin levels via inhibition of kinin breakdown and have been shown in experimental studies to augment early protection afforded by PC. A role for bradykinin in eliciting delayed PC has not so far been identified. METHODS: We used a two-day protocol. On day 1 (closed chest), pigs were either sham-operated (group 1) or preconditioned, using balloon catheter inflation of the left anterior descending (LAD) coronary artery, with either a full (4 x 5 min PC, group 2) or subthreshold PC stimulus (2 x 2 min PC, group 3). Additional groups were pre-treated with perindoprilat (0.06 mg/kg i.v.) before sham (group 4) or subthreshold PC (group 5). On day 2 (open chest), all pigs were subjected to 40 min occlusion of the LAD followed by 3 h of reperfusion. Infarct size was determined by tetrazolium staining. RESULTS: Group 1 had a mean infarct size of 42.8+/-3.2% of the risk zone. Preconditioning with 4 x 5 min reduced the infarct size to 19.5+/-3.9% (p < 0.05). Groups 3 and 4 had infarct sizes not statistically different from group 1. However, combining perindoprilat with subthreshold PC resulted in a significant limitation of the infarction (18.4+/-3.1% p < 0.05), comparable with group 2. CONCLUSIONS: This is the first study to show that ACE inhibition can augment a mild ischemic stimulus to induce a protected state 24 h later.

Veteran athletes exercise at higher maximum heart rates than are achieved during standard exercise (stress) testing.

OBJECTIVE: The stress electrocardiogram (sECG) is routinely used to screen individuals for underlying cardiac pathology before an exercise programme is prescribed. The underlying assumption is that the cardiac responses elicited during the sECG test are similar to those achieved during participation in sporting activities. However, this premise may be incorrect since the physical demands of different modes of exercise vary substantially. DESIGN: Ten veteran league squash players (LSP), 10 social squash players (SSP), 10 league runners (LR), 10 social runners (SR) and 10 sedentary individuals (SED) were recruited for the study. All subjects completed a lifestyle questionnaire, a full medical examination and a routine sECG. Thereafter each subject's heart rate (HR) was monitored on two separate occasions while participating in sporting activity. RESULTS: No sECG exercise-induced abnormalities were observed, although five subjects showed resting abnormalities. Maximal HR during the sECG, and maximal and mean HR during the field tests, were not significantly different between groups. However, maximal HR was significantly higher in all groups during their sporting activities than during stress testing in the laboratory (P < 0.01). CONCLUSIONS: Maximal HR in veteran athletes during specific sporting activities was significantly higher than that attained during a routine sECG. This finding was not sport-specific, nor was it related to the level of competitiveness of the trial participants. These data show that a routine sECG is a submaximal test of exercise performance, and should be interpreted as such.

Kinetics of purified protein derivative (PPD) proliferation reflects underlying suppressor mechanisms revealed by limiting dilution analysis (LDA) in patients with extrapulmonary tuberculosis (TB).

Mononuclear leucocytes from the blood (PBML) and effusion (EML) of patients undergoing pericardiocentesis were assayed for proliferative response to purified protein derivative of Mycobacterium tuberculosis (PPD). Of the 23 patients tested, 10 had culture-positive tuberculous effusions, while 13 had non-tuberculous aetiologies. Three different kinetic responses were identified: (i) accelerated responses (found in 70% of EML from patients with culture-positive tuberculous effusions); (ii) 'flat' responses (found in 10% of EML from patients with culture-positive tuberculous effusions); and (iii) normal kinetic responses. These differences in kinetic response may reflect underlying immune mechanisms important in the immunopathogenesis of TB. In order to address this possibility we performed LDA on a selection of patients with culture-positive extrapulmonary TB: three patients with accelerated responses, two with normal responses, and one with a 'flat' response. The results confirm the previously reported accumulation of PPD-specific responder cells in the effusion of patients with TB. Cell-mediated suppressor mechanisms (as shown by 'V'-shaped LDA curves) were found in the blood of one patient and the effusion of another. In both cases 'flat' PPD-proliferative responses were observed. However, the LDA data also suggested the presence of in vivo mechanisms limiting the clonal burst size. Thus it appears that immune responses in extrapulmonary TB are influenced by an array of inhibitory mechanisms, modulation of which may influence the outcome of infection.

Memory lymphocytes from tuberculous effusions: purified protein derivative (PPD) stimulates accelerated activation marker expression and cell cycle progression.

Accelerated PPD-specific proliferation and generation of CD4+ cytotoxic effectors by mononuclear leucocytes (MNL) from tuberculous effusions (EMNL) has been previously reported by our laboratory. In order to explore the contribution of the state of activation of MNL to accelerated reactivity, EMNL and peripheral blood (PB)MNL from seven patients with tuberculosis were assessed both ex vivo and after PPD stimulation. Flow cytometry revealed no difference in the activation state (IL-2 receptor and HLA-DR expression) or cell cycle progression ex vivo. However, CD4+ CD29+ memory T cells were accumulated in EMNL compared with PBMNL. In vitro stimulation of EMNL with PPD resulted in accelerated expression of activation markers and progression through the cell cycle (peak after 4 days), whilst PBMNL exhibited normal activation kinetics (peak after 7 days). Accelerated reactivity could not be accounted for by quantitative differences in effusion CD4+ CD29+ memory T cells compared with blood, but may be due to a qualitative difference in effusion memory T cells, which are shown to be in a postactivation state of differentiation. T cells entering S and G2/M phases of the cell cycle were largely of the activated memory phenotype. Activation marker expression occurred in association with up-regulation of CD4 antigen expression on the surface of EMNL. Thus accelerated expression of activation markers and cell cycle progression by CD4+ CD29+ memory T cells may in part account for accelerated PPD reactivity in tuberculous effusions.

Giant right coronary artery aneurysm with fistulous connection to the coronary sinus: diagnosis and management.

This report describes the case of a giant aneurysmal right coronary artery connecting to the coronary sinus near its opening into the right atrium in a 70-year-old woman who presented with a recent onset of congestive heart failure. By coincidence, a secundum atrial septal defect was also present. The diagnosis and surgical management of this uncommon pathology are described.

Apical hypertrophic cardiomyopathy. A case report.

The clinical, ECG and angiographic features of apical hypertrophic cardiomyopathy in a 24-year-old white man are reported. Only 4 non-Oriental cases have so far been described and the present case is the second from South Africa. Attention is drawn to the possibility that there are two distinct types of apical hypertrophic cardiomyopathy.