Sustained cardiac programming by short-term juvenile exercise training in male rats.

KEY POINTS: Cardiac hypertrophy following endurance-training is thought to be due to hypertrophy of existing cardiomyocytes. The benefits of endurance exercise on cardiac hypertrophy are generally thought to be short-lived and regress to sedentary levels within a few weeks of stopping endurance training. We have now established that cardiomyocyte hyperplasia also plays a considerable role in cardiac growth in response to just 4 weeks of endurance exercise in juvenile (5-9 weeks of age) rats. The effect of endurance exercise on cardiomyocyte hyperplasia diminishes with age and is lost by adulthood. We have also established that the effect of juvenile exercise on heart mass is sustained into adulthood. ABSTRACT: The aim of this study was to investigate if endurance training during juvenile life 'reprogrammes' the heart and leads to sustained improvements in the structure, function, and morphology of the adult heart. Male Wistar Kyoto rats were exercise trained 5 days week-1 for 4 weeks in either juvenile (5-9 weeks of age), adolescent (11-15 weeks of age) or adult life (20-24 weeks of age). Juvenile exercise training, when compared to 24-week-old sedentary rats, led to sustained increases in left ventricle (LV) mass (+18%; P < 0.05), wall thickness (+11%; P < 0.05), the longitudinal area of binucleated cardiomyocytes (P < 0.05), cardiomyocyte number (+36%; P < 0.05), and doubled the proportion of mononucleated cardiomyocytes (P < 0.05), with a less pronounced effect of exercise during adolescent life. Adult exercise training also increased LV mass (+11%; P < 0.05), wall thickness (+6%; P < 0.05) and the longitudinal area of binucleated cardiomyocytes (P < 0.05), despite no change in cardiomyocyte number or the proportion of mono- and binucleated cardiomyocytes. Resting cardiac function, LV chamber dimensions and fibrosis levels were not altered by juvenile or adult exercise training. At 9 weeks of age, juvenile exercise significantly reduced the expression of microRNA-208b, which is a known regulator of cardiac growth, but this was not sustained to 24 weeks of age. In conclusion, juvenile exercise leads to physiological cardiac hypertrophy that is sustained into adulthood long after exercise training has ceased. Furthermore, this cardiac reprogramming is largely due to a 36% increase in cardiomyocyte number, which results in an additional 20 million cardiomyocytes in adulthood.

Effect of interscalene anaesthesia on cerebral oxygen saturation.

Interscalene blockade (ISB) is commonly associated with Horner's syndrome, indicating spread of injectate to the cervical sympathetic chain. Cervical sympathetic nerve activity (SNA) is believed to influence cerebral autoregulation, and a decrease in sympathetic tone may alter cerebral blood flow (CBF). This study investigated whether ISB influenced CBF in patients undergoing shoulder surgery. Patients (n=30) scheduled for elective shoulder arthroscopy were recruited. Cerebral oxygen saturation (ScO(2)) of the left and right frontal cortices was continuously measured during ISB administration, sedation and anaesthetic induction. Baseline ScO(2) was similar in blocked and unblocked sides (74 ± 5% and 73 ± 5% respectively, P=0.70). ScO(2) decreased with sedation (-3 ± 3% and -4 ± 3%, P=0.93), and increased with pre-oxygenation and general anaesthesia (P <0.01). Following ISB there was no change in ScO(2) between blocked and unblocked sides (P=0.18), or any difference between right- or left-sided ISB. ISB is not associated with an increase in CBF as indicated by ScO(2), despite the presence of Horner's syndrome.

Effect of phenylephrine on the haemodynamic state and cerebral oxygen saturation during anaesthesia in the upright position.

BACKGROUND: The upright sitting or beachchair position is associated with hypotension, risk of cerebral hypoperfusion, and cerebral injury. We hypothesized that by increasing arterial pressure with phenylephrine administration, cerebral perfusion, and postoperative recovery would be improved. METHODS: Thirty-four patients undergoing elective shoulder surgery were randomized to receive either saline or phenylephrine infusion (PE) 5 min before being placed in the upright position. Simultaneous measurements of mean arterial pressure, cerebral oxygen saturation, middle cerebral artery velocity, and cardiac function using transthoracic echocardiography were made. Postoperative neurocognitive function was assessed. RESULTS: At the commencement of PE, mean (SD) cerebral oxygen saturation significantly decreased from 77 (10) to 67 (13)% (P=0.02), and further to 59 (11) % on upright positioning. The level of cerebral saturation upright was not significantly different to patients receiving saline (P=0.07), with values remaining at room-air levels. Middle cerebral artery blood velocity increased by 20% (P=0.04). Phenylephrine prevented hypotension in the upright position primarily by maintaining preload and increasing systemic vascular resistance (P=0.01), and was associated with a decrease in cardiac output. No postoperative neurocognitive dysfunction was identified. CONCLUSIONS: Despite maintaining arterial pressure with phenylephrine, cerebral desaturation occurred with upright positioning. Cerebral oxygen saturation can provide a valuable endpoint when evaluating the effect of vasopressor therapy on cerebral perfusion.

The effect of the sitting upright or 'beachchair' position on cerebral blood flow during anaesthesia for shoulder surgery.

The sitting upright or 'beachchair' position is commonly used for shoulder arthroscopic surgery. There is a theoretical concern that anaesthetised patients placed in this posture are at risk of reduced cerebral blood flow (CBF), especially if there is associated hypotension. This study investigated the effect of anaesthetic-induced hypotension on estimated cerebral blood flow in patients placed in the beachchair position for shoulder surgery. Forty patients were randomised to either sedation (propofol infusion 10 to 20 mg x hour 1, n = 20) or general anaesthesia using sub minimum alveolar concentration of sevoflurane (n = 20). All patients received an interscalene brachial plexus regional block. Internal carotid artery blood flow was measured using the time averaged velocity of the spectral Doppler waveform, and was then used as an estimate of global CBF. Following a pre-anaesthesia study, measurement of internal carotid artery blood flow was made before and after beachchair positioning, and at five-minute intervals during surgery. Beachchair positioning during general anaesthesia significantly decreased the mean arterial pressure (34 +/- 10 mmHg) compared to sedation (4 +/- 2 mmHg, P < 0.01), and vasopressor therapy was required more often. However, CBF remained constant in both anaesthetised (P = 0.83) and sedated patients (P = 0.68) despite beachchair positioning, and the fall in mean arterial pressure in the anaesthetised patients. There was no significant difference in CBF between groups (P = 0.91). These findings indicate that in patients in the beachchair position receiving sevoflurane anaesthesia, CBF is maintained when mean arterial pressure is above 70 mmHg, consistent with intact autoregulation.

High thoracic epidural analgesia for cardiac surgery: an audit of 874 cases.

Despite clinical use for over 10 years, high thoracic epidural analgesia for cardiac surgery remains controversial, due to a perceived increased risk of epidural haematoma resulting from anticoagulation for cardiac pulmonary bypass. There are no sufficiently large randomised studies to address this question and few large case series reported. For this reason, we conducted an audit of neurological complications related to high thoracic epidural analgesia during cardiac surgery in our institution between 1998 and end 2005. During this period 874 patients received epidural analgesia. There were no neurological complications attributable to epidural use. Our findings suggest that major neurological complications related to high thoracic epidural use during cardiac surgery are rare.

Anatomical study of the brachial plexus using surface ultrasound.

The aim of this study was to define the anatomy relevant to brachial plexus regional anaesthesia and to identify the extent of variation between individuals. Surface ultrasound examination of the brachial plexus was performed on twenty volunteers. In the axilla there was considerable individual variation in the location of the median, radial and ulnar nerves in relation to the axillary artery. There was often more than one venous structure in this region, which was easily compressed by surface palpation. In the supraclavicular region, neural elements were located inferiorly to the subclavian artery in two volunteers. In one volunteer, a vein was identified between nerve trunks in the interscalene region. These findings indicate that the anatomical variation is considerable, even within the relatively small sample studied. For this reason, use of surface ultrasound may lead to increased success of brachial plexus regional anaesthesia and a decreased risk of intravascular injection.

Alfentanil infusion as a component of intravenous anaesthesia for coronary artery bypass surgery with "fast-track" recovery.

Alfentanil and propofol total intravenous anaesthesia was assessed in 25 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). A manually controlled alfentanil infusion, calculated from estimated lean body mass and published pharmacokinetic data, was effective in achieving target plasma concentrations, while the "Diprifusor" system was used to vary propofol target concentrations according to changes in haemodynamics and anaesthetic requirement. The effects of CPB on alfentanil plasma concentrations were offset by changes in protein binding and free-fraction of the drug. With the use of only two target plasma concentrations for alfentanil (changed after CPB), a pre-determined infusion profile ensured effective plasma concentrations during surgery and concentrations unlikely to inhibit extubation within six hours of sternal closure.

Shape and movement of the interatrial septum predicts change in pulmonary capillary wedge pressure.

We aimed to assess whether movement of the interatrial septum predicts change in pulmonary capillary wedge pressure (PCWP). In 71 patients undergoing cardiac surgery, the interatrial septum was categorised by its shape and movement using transesophageal echocardiography. Fixed curvature (FC) was identified by bowing of the interatrial septum from left to right throughout the cardiac cycle, mid-systolic reversal (MSR) by minimal septal movement and transient reversal (right to left) during mid-systole, and mid-systolic buckling (MSB) by marked movement and buckling of the septum during mid-systole. These were compared with PCWP. Sensitivity and interobserver reliability was studied with continuous PCWP and TEE measurement during a period of acute volume alteration in 10 additional patients. Interatrial septal movement predicted PCWP, with mean PCWP (95% confidence intervals) for FC, 18.1 mmHg (16.7 to 19.6), MSR 13.2 mmHg (12.5 to 13.8) and MSB, 9.9 mmHg (9.0 to 10.7) mmHg. The mean PCWP at which a change in pattern occurred was 8.9 mmHg (8.3 to 9.6) for MSR to MSB, and 10.9 mmHg (10.1 to 11.8) for MSR to FC (p<0.001). There was no significant difference in mean values for all three observers. Movement of the interatrial septum predicts change in PCWP.

Routine immediate extubation after cardiac operation: a review of our first 100 patients.

BACKGROUND: Early extubation after cardiac operation is an important aspect of fast-track cardiac anesthesia. Immediate extubation is an extension of this concept. We describe a technique that allows immediate extubation in the majority of patients. METHODS: To allow rapid emergence, anesthesia was modified from a high-dose opioid technique to intravenous propofol anesthesia supplemented with sevoflurane. Normothermic cardiopulmonary bypass was used with routine intermittent antegrade and retrograde tepid blood cardioplegia. High thoracic epidural analgesia was used to facilitate immediate extubation in the majority of patients. Contraindications to immediate extubation were prolonged cardiopulmonary bypass (CPB) (>2.5 hours), hemodynamic instability, uncontrolled bleeding, morbid obesity, severe pulmonary hypertension, congestive cardiac failure, or if the operation was emergent. RESULTS: Of 109 consecutive patients, 100 were immediately extubated (92%). No patient required reintubation within the first 24 hours after operation. One patient required reintubation 3 days after operation for sputum retention, and 2 patients required reoperation. There was no mortality and the incidence of perioperative morbidity was low. CONCLUSIONS: Immediate extubation after cardiac operation can be safely achieved and is possible in a majority of patients.