Haemoglobin Levels in Acute Coronary Syndrome Patients Admitted in Cardiology Intensive Care Units in a Tertiary Care Hospital.

OBJECTIVE: Epidemiology of abnormal haemoglobin levels and its association with severity of coronary artery disease in Indian patients is uncertain. This prospective observational study was conducted to determine the haemoglobin levels in acute coronary syndrome (ACS) patients and the association of anaemia with the severity of coronary artery disease (CAD) on coronary angiography (CAG). METHODS: The patients diagnosed with ACS (ST-elevated and non-elevated MI, unstable angina) based on ECG and cardiac enzymes and admitted in cardiology ICU were enrolled in the study after fulfilling study criteria and the baseline haemoglobin level was recorded. The severity of coronary disease of patients who underwent coronary angiography was recorded. RESULTS: A total of 162 patients were enrolled for the study. The overall haemoglobin of patients was 11.99 ± 2.24 g/dl with 12.46 ± 2.33 g/dl in males and 11.17 ± 1.82 g/dl in females (p < 0.05). Anaemia was found in 62.96% patients with no significant gender difference (p > 0.05), however abnormal haemoglobin level (Hb > 16g/dl) was found exclusively in 7.7% males. One hundred one patients underwent coronary angiography and anaemia was present in 60 patients (58.82%) and absent in 41 (40.59%). The difference in mean haemoglobin levels in anaemic patients with single, double, and triple vessel disease was significant (p < 0.05) and corresponding levels in non-anaemic patients were insignificant (p > 0.05). A weak correlation was observed between the haemoglobin level of patients and the percentage of obstruction in CAG (r = 0.26). The odds of having triple vessel disease in anaemic patient are 1.77 (95% CI 0.71 to 4.43). However, the association between anaemia and the severity of coronary artery disease was statistically found to be non-significant. CONCLUSION: The mean haemoglobin levels decreased as the severity of CAD increased in CAG, however the association was not established between anaemia and the severity of coronary artery disease statistically.

Human experimental pain models: A review of standardized methods in drug development.

Human experimental pain models are essential in understanding the pain mechanisms and appear to be ideally suited to test analgesic compounds. The challenge that confronts both the clinician and the scientist is to match specific treatments to different pain-generating mechanisms and hence reach a pain treatment tailored to each individual patient. Experimental pain models offer the possibility to explore the pain system under controlled settings. Standardized stimuli of different modalities (i.e., mechanical, thermal, electrical, or chemical) can be applied to the skin, muscles, and viscera for a differentiated and comprehensive assessment of various pain pathways and mechanisms. Using a multimodel-multistructure testing, the nociception arising from different body structures can be explored and modulation of specific biomarkers by new and existing analgesic drugs can be profiled. The value of human experimental pain models is to link animal and clinical pain studies, providing new possibilities for designing successful clinical trials. Spontaneous pain, the main compliant of the neuropathic patients, but currently there is no human model available that would mimic chronic pain. Therefore, current human pain models cannot replace patient studies for studying efficacy of analgesic compounds, although being helpful for proof-of-concept studies and dose finding.

A simple thermal pain model for the evaluation of analgesic activity in healthy subjects.

OBJECTIVE: Assessment of the analgesic effect of an agent in an experimental pain model permits a level of control not possible in a clinical pain setting and is an ideal approach for evaluation of analgesic drugs. The aim of the present study was to establish a simple and reliable method of producing experimental pain, which can be used for screening of various analgesic agents. MATERIALS AND METHODS: The standardized method was followed in all cases, by recording thermal pain threshold in seconds in 24 healthy volunteers using hot air source at two different speeds, which is equipped in an acrylic-made chamber adjustable to three different levels. Reproducibility of the test procedure was evaluated by recording the thermal threshold parameter by a single observer on two sessions (interday reproducibility) and second observer on one session (interobserver reproducibility) separately. Validity of model was further tested by evaluating the analgesic effect of tramadol on 12 healthy volunteers. RESULTS: Thermal pain model was found to produce low variability with coefficient of variation (CV) less than 10%. Interobserver and interday reproducibility were very good, as shown by Bland-Altman plot, with most of the values within ± 2SD. There was a significant increase in pain threshold time with use of tramadol as compared to placebo which was statistically significant (P < 0.05). CONCLUSION: The newly developed pain model offers a stable and sensitive method for the early assessment of analgesic activity.

A simple cold pressure technique for the evaluation of analgesic drugs in healthy subjects.

AIM: An experimental pain model which is sensitive and reproducible would be a useful pharmacological tool both for existing and new drugs. The aim of the present study was to establish a simple and reliable method of producing experimental pain which can be used for screening of analgesic agents. MATERIALS AND METHODS: The method was standardized by recording pain threshold and pain tolerance values in 24 healthy volunteers. Reproducibility of the test procedure was evaluated by recording the pain threshold and pain tolerance values by a single observer on two sessions (inter-day reproducibility), and second observer in one session (inter-observer reproducibility), separately. Validity of the model was further tested by evaluating the analgesic effect of tramadol in 12 healthy volunteers. RESULTS: Cold pain model was found to produce low variability with coefficient of variation less than 15%. Inter-observer and inter-day reproducibility was very good as shown by Bland - Altman plot with most of the values within ± 2SD. Analgesic activity by Tramadol was statistically different from placebo (P < 0.05). CONCLUSION: The newly developed pain model offers a stable and sensitive method for the early assessment of analgesic activity.

Effect of beta-1-blocker, nebivolol, on central aortic pressure and arterial stiffness in patients with essential hypertension.

INTRODUCTION: Blood pressure (BP) reduction is the major determinant of benefit provided by antihypertensive treatment. Although different drugs reduce peripheral BP to some extent, there may be a significant difference in their effect on central BP reduction. It has been shown that beta-blockers are efficient in reducing peripheral, but not central BP. This study was done to assess the effect of beta-1-blocker, nebivolol, in patients with essential hypertension on central aortic pressures and arterial stiffness. MATERIALS AND METHODS: In this single arm, open-labeled study, 13 patients were given nebivolol, 5 mg orally once daily for 15 days. Primary outcome was change in central aortic pressure, and other measures of efficacy included changes in brachial BP, augmentation index (AIx%), AIx%@75 HR, augmentation pressure (AP), heart rate (HR), and carotid femoral pulse wave velocity (PWVcf). RESULTS: Nebivolol 5 mg significantly reduced central aortic pressures [systolic BP, 131.5-111.6 mmHg; diastolic BP, 96.3-81.7 mmHg; Mean Arterial Pressure (MAP), 111.3-94.0 mmHg (all P<0.0001), and Pulse Pressure (PP), 35.2-29.7 mmHg (P<0.01)]. AIx%@75 HR reduced from 29 to 21.6 (P<0.001) and PWVcf reduced from 8.6 to 7.2 m/s (P<0.001). One subject was lost to followup. CONCLUSION: Nebivolol 5 mg demonstrated antihypertensive efficacy in patients with essential hypertension by reducing not only peripheral brachial pressures, but also significantly reducing central aortic pressures, augmentation index, and carotid femoral pulse wave velocity, which is the marker of arterial stiffness.

Development of a simple radiant heat induced experimental pain model for evaluation of analgesics in normal healthy human volunteers.

OBJECTIVE: Human experimental pain models help to understand the mechanism of the painful conditions and can also be adopted to test analgesic efficacy of drugs. In early phases, the clinical development of new analgesics is hindered due to the lack of reliable tests for the experimental pain models. In the present study, we have developed and validated a simple radiant heat pain model which can be used for future screening of various analgesic agents. MATERIALS AND METHODS: We have standardized the thermal pain model by recording pain threshold and pain tolerance time in seconds at three different intensities and levels in 24 healthy subjects. Reproducibility of the test procedure was evaluated by recording the pain parameters by two observers on three consecutive days. Validity of model was further tested by evaluating the analgesic effect of tramadol. RESULTS AND CONCLUSIONS: Use of radiant heat pain model with high intensity and short level was found to produce low variability with coefficient of variation less than 5%. Interobserver and interperiod reproducibility was very good as shown by Bland - Altman plot; with most of the values within ± 2SD. Tramadol produced statistically significant increase in pain threshold time. The newly developed pain model produces a type of experimental pain which is responsive to analgesic effects of tramadol at clinically relevant doses.