The enigma of Pacini's Vibrio cholerae discovery.

During the 1854 cholera outbreak in Florence, Italy, Filippo Pacini documented that the cause of the infection was a bacterium. This conclusion was also independently reached by John Snow during the 1854 cholera outbreak in London. By using an epidemiological method, Snow found that the infection spread through a polluted water network. Snow identified a water pump as the source of the disease. After removing the infected handle of this pump, the cases of cholera rapidly began to decrease. A microscopic examination of the water showed organic impurities but no bacteria. This discovery was ignored during Snow's lifetime. In contrast, through microscopy during the autopsies of cholera victims, Pacini observed that the disruption of their intestinal mucosa was closely associated with millions of the bacteria that he called Vibrio cholerae. Via histological techniques, Pacini detected that intestinal mucosa reabsorption dysfunction was the cause of debilitating diarrhoea, vomiting, severe dehydration and death. Nevertheless, his discovery of Vibrio cholerae was ignored during Pacini's lifetime. A survey of Pacini's autographic manuscripts suggests that Pacini and Snow may have shared mutual knowledge within their respective seminal papers. This survey also facilitates, for the first time, the creation of maps that illustrate the worldwide distribution of Pacini's cholera papers from 1854 to 1881. The consistent neglect of Pacini's discovery remains a true enigma.

Nitrate-induced paradoxical ischemia predicts adverse outcomes in elderly patients with healed myocardial infarcts.

BACKGROUND: It is well known that nitrates can induce paradoxical myocardial ischemia. METHODS AND RESULTS: Fifty patients (median age 73 years; range 67 to 78 years; 80% male) with healed myocardial infarcts were selected. All patients underwent resting single-photon emission computed tomography (SPECT) and resting baseline gated-SPECT using sestamibi or thallium-201 after the sublingual administration of 5 mg isosorbide dinitrate (ISD). Forty-eight per cent (24 of 50) of the patients demonstrated ISD-induced peri-infarct ischemia as observed by SPECT. Compared with patients without ISD-induced ischemia, patients with ISD-induced ischemia presented larger infarcts as determined by the extent of perfusion defects (mean [± SD] 27±12 pixels versus 11±9 pixels; P<0.0001), lower ejection fractions (39±17% versus 50±15%; P<0.02) and a higher incidence of severe coronary artery disease (P<0.04). At five years, the survival probability on Kaplan-Meier analysis was 42% and 96% for patients with and without ISD-induced ischemia, respectively (HR 5.6 [95% CI 1.6 to 20]; P=0.009). CONCLUSIONS: Nitrates may have low efficacy in improving blood flow through the coronary vessels that supply large myocardial infarcts with high-resistance microvascular damage. At the same time, nitrates induce dilation and blood pressure decrease in remotely patent or mildly stenotic vessels. The blood pressure gradient elicited between the high- and low-resistance coronary vessels may provide the force for a blood flow steal from the viable zones of the infarct toward the healthy myocardium. The resultant nitrate-induced paradoxical ischemia could be a silent marker of myocardial instability and adverse outcomes in elderly patients with healed myocardial infarcts.

A novel clinical indicator using cardiac technetium-99m sestamibi kinetics for evaluating cardiotoxicity in cancer patients treated with multiagent chemotherapy.

BACKGROUND: Multiagent chemotherapy (MCT) has mitochondrial targets. Since technetium-99m-sestamibi (MIBI) is a marker of mitochondrial metabolism, cardiac MIBI uptake and MIBI washout rate (%WR) may detect MCT-induced cardiotoxicity. METHODS: In 16 cancer patients on MCT for 10 months and in 14 non-cancer controls, cardiac MIBI uptake between early (30 min) and delayed (3 hours) post-injection planar images was measured as counts per pixel (cpp). The MIBI cardiac %WR was also measured. RESULTS: When MCT patients and controls were compared, early and cardiac delayed MIBI uptake were greater in MCT patients (45 ± 12 cpp vs. 30 ± 4 cpp; p <0.04) and (30 ± 8 cpp vs. 25 ± 2 cpp; p < 0.02), but % WR did not change (12 ± 4% vs. 13 ± 3%; p = ns). However, in the MCT patients, the MIBI cardiac %WR was more rapid because it was obtained at the same time as in the control patients but from a greater amount of MIBI cardiac uptake. On 36-months follow-up, only MCT patients died of cardiac death. Overall survival risk parameters, only delayed cardiac MIBI uptake (Odds ratio = 1.7, p<0.001) and early cardiac MIBI uptake (Odds ratio = 1.2, p<0.02) were found to be significantly associated with cardiac mortality. CONCLUSIONS: In experimental studies, anticancer drugs elicit mitochondrial membrane hyperpolarization with passive cardiac MIBI uptake. In MCT patients, the increased cardiac MIBI uptake and rapid %WR compared with controls may reflect mitochondrial membrane dysfunction, pre-clinical cardiotoxicity and thus poor prognosis.

Inducible myocardial ischaemia and anomalous origin of the right coronary artery coursing between the aorta and pulmonary artery: a rare, sinister entity.

The authors report the case of a 49-year-old man with episodes of chest discomfort. Exercise/rest single-photon emission tomography (SPECT) with technetium-99m sestamibi (MIBI) revealed inferior and septal myocardial ischaemia, and MIBI anterior reverse redistribution, representing damaged myocardium. Cardiac tomography documented anomalous origin of the right coronary artery (ARCA) arising from the left sinus of valsalva coursing between the aorta and pulmonary artery. Myocardial ischaemia and myocardial damage revealed by SPECT are related to the transient coronary flow reduction elicited by the compression of the ARCA that is produced by the great arteries during exercise. The ARCA is a rare condition, but may cause myocardial infarction and sudden death. ß-blockers and dihydropyridine calcium-channel blockers may provide cardioprotection from inducible myocardial ischaemia. However, in case of failure of medical cardioprotection, relocation of the ARCA to the appropriate aortic sinus and coronary bypass grafting could be considered as the best options.

Depressed Exercise Peak Ejection Rate Detected on Ambulatory Radionuclide Monitoring Reflects End-Stage Cardiac Inotropic Reserve and Predicts Mortality in Ischaemic Cardiomyopathy.

BACKGROUND: Fifteen patients with ischaemic cardiomyopathy and inducible ischaemia were studied to determine the mechanisms of mortality. Failure of the contractile reserve during daily life activities may reflect a prognostic index. METHODS: Single photon emission cardiac tomography and radionuclide ambulatory monitoring (Vest) data were analysed in all patients with a 7-year follow-up. RESULTS: At peak exercise on Vest, the 7 non-survivors (N-SURV) showed worse peak ejection rates (PERs) and ejection fractions (EFs) compared with the 8 survivors (SURV), (2 ± 0.6 vs. 3.3 ± 0.7; end-diastolic volumes (EDVs), P < 0.003), and (34 ± 10% vs. 50 ± 13%; P < 0.02), respectively. However, exercise peak filling rates (PFRs) (1.9 ± 0.6 vs. 2.7 ± 0.9; EDVs/s) and exercise heart rates (HRs), (97 ± 17 vs. 106 ± 10), did not differ between the two groups (P > 0.05). In SURV, exercise PERs, which represented rapid left ventricular (LV) emptying, were significantly correlated with exercise PFRs, representing rapid LV filling, (r = 0.71, P < 0.04) but not in N-SURV (r = 0.66, P > 0.05). Among SURV, the Frank-Starling mechanism was thus preserved but not in N-SURV. Upon Cox analysis, overall LV function parameters, exercise PER was the only predictive measure associated with mortality (b = - 0.018, relative hazard ratio = 0.98, P = 0.02). CONCLUSIONS: Exercise PER reduced values reflected failure of the Frank-Starling mechanism, the incapacity of the heart to perform rapid contractile adaptations to daily life activities and a poor prognosis.

A rare cause of abdominal angina.

The authors report a case of a young male with median arcuate ligament syndrome (MALS). An abnormally low insertion of the median arcuate ligament fibres caused extrinsic compression and stenosis of the coeliac trunk. However, partial dissection of ligament fibres by laparoscopic surgery did not relieve abdominal angina. Multidetector CT confirmed that MALS did not differ from the preoperative scan. The arcuate ligament compressed the coeliac trunk on expiration, thereby eliciting occlusion of the coeliac trunk. Inspiration induced decompression of the ligament with partial release of occlusion of the coeliac trunk. This leads to hypo-perfusion of intestinal organs and abdominal angina. Considering the severe impairment of quality of life, open surgery for decompression of the coeliac trunk with vascular reconstruction is a reasonable option.