Exaggerated Peripheral and Systemic Vasoconstriction During Trauma Recall in Posttraumatic Stress Disorder: A Co-Twin Control Study.

BACKGROUND: Individuals with posttraumatic stress disorder (PTSD) face an increased risk of cardiovascular disease, but the mechanisms linking PTSD to cardiovascular disease remain incompletely understood. We used a co-twin control study design to test the hypothesis that individuals with PTSD exhibit augmented peripheral and systemic vasoconstriction during a personalized trauma recall task. METHODS: In 179 older male twins from the Vietnam Era Twin Registry, lifetime history of PTSD and current (last month) PTSD symptoms were assessed. Participants listened to neutral and personalized trauma scripts while peripheral vascular tone (Peripheral Arterial Tone ratio) and systemic vascular tone (e.g., total vascular conductance) were measured. Linear mixed-effect models were used to assess the within-pair relationship between PTSD and vascular tone indices. RESULTS: The mean age of participants was 68 years, and 19% had a history of PTSD. For the Peripheral Arterial Tone ratio analysis, 32 twins were discordant for a history of PTSD, and 46 were discordant for current PTSD symptoms. Compared with their brothers without PTSD, during trauma recall, participants with a history of PTSD had greater increases in peripheral (ß = -1.01, 95% CI [-1.72, -0.30]) and systemic (total vascular conductance: ß = -1.12, 95% CI [-1.97, -0.27]) vasoconstriction after adjusting for cardiovascular risk factors. Associations persisted after adjusting for antidepressant medication use and heart rate and blood pressure during the tasks. Analysis of current PTSD symptom severity showed consistent results. CONCLUSIONS: PTSD is associated with exaggerated peripheral and systemic vasoconstrictor responses to traumatic stress reminders, which may contribute to elevated risk of cardiovascular disease.

Haemodynamic characteristics of COVID-19 patients with acute respiratory distress syndrome requiring mechanical ventilation. An invasive assessment using right heart catheterization.

AIMS: Interstitial pneumonia due to coronavirus disease 2019 (COVID-19) is often complicated by severe respiratory failure. In addition to reduced lung compliance and ventilation/perfusion mismatch, a blunted hypoxic pulmonary vasoconstriction has been hypothesized, that could explain part of the peculiar pathophysiology of the COVID-19 cardiorespiratory syndrome. However, no invasive haemodynamic characterization of COVID-19 patients has been reported so far. METHODS AND RESULTS: Twenty-one mechanically-ventilated COVID-19 patients underwent right heart catheterization. Their data were compared both with those obtained from non-mechanically ventilated paired control subjects matched for age, sex and body mass index, and with pooled data of 1937 patients with 'typical' acute respiratory distress syndrome (ARDS) from a systematic literature review. Cardiac index was higher in COVID-19 patients than in controls [3.8 (2.7-4.5) vs. 2.4 (2.1-2.8) L/min/m2 , P < 0.001], but slightly lower than in ARDS patients (P = 0.024). Intrapulmonary shunt and lung compliance were inversely related in COVID-19 patients (r = -0.57, P = 0.011) and did not differ from ARDS patients. Despite this, pulmonary vascular resistance of COVID-19 patients was normal, similar to that of control subjects [1.6 (1.1-2.5) vs. 1.6 (0.9-2.0) WU, P = 0.343], and lower than reported in ARDS patients (P < 0.01). Pulmonary hypertension was present in 76% of COVID-19 patients and in 19% of control subjects (P < 0.001), and it was always post-capillary. Pulmonary artery wedge pressure was higher in COVID-19 than in ARDS patients, and inversely related to lung compliance (r = -0.46, P = 0.038). CONCLUSIONS: The haemodynamic profile of COVID-19 patients needing mechanical ventilation is characterized by combined cardiopulmonary alterations. Low pulmonary vascular resistance, coherent with a blunted hypoxic vasoconstriction, is associated with high cardiac output and post-capillary pulmonary hypertension, that could eventually contribute to lung stiffness and promote a vicious circle between the lung and the heart.

Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues.

Altered vascular tone responsiveness to pathophysiological stimuli contributes to the development of a wide range of cardiovascular and metabolic diseases. Endothelial dysfunction represents a major culprit for the reduced vasodilatation and enhanced vasoconstriction of arteries. Adipose (fat) tissues surrounding the arteries play important roles in the regulation of endothelium-dependent relaxation and/or contraction of the vascular smooth muscle cells. The cross-talks between the endothelium and perivascular adipose tissues can be assessed ex vivo using mounted blood vessels by a wire myography system. However, optimal settings should be established for arteries derived from animals of different species, ages, genetic backgrounds and/or pathophysiological conditions.

Concurrent activation of multiple vasoactive signaling pathways in vasoconstriction caused by tubuloglomerular feedback: a quantitative assessment.

Tubuloglomerular feedback (TGF) describes the negative relationship between (a) NaCl concentration at the macula densa and (b) glomerular filtration rate or glomerular capillary pressure. TGF-induced vasoconstriction of the afferent arteriole results from the enhanced effect of several vasoconstrictors with an effect size sequence of adenosine = 20-HETE > angiotensin II > thromboxane = superoxide > renal nerves > ATP. TGF-mediated vasoconstriction is limited by the simultaneous release of several vasodilators with an effect size sequence of nitric oxide > carbon monoxide = kinins > adenosine. The sum of the constrictor effects exceeds that of the dilator effects by the magnitude of the TGF response. The validity of the additive model used in this analysis can be tested by determining the effect of combined inhibition of some or all agents contributing to TGF. Multiple independent contributors to TGF are consistent with the variability of TGF and of the factors contributing to TGF resetting.

Endothelial function assessment: flow-mediated dilation and constriction provide different and complementary information on the presence of coronary artery disease.

AIMS: A number of risk factors for atherosclerosis have been identified, but it remains difficult, on an individual patient basis, to predict how these factors interact in determining the development of coronary artery disease (CAD). It also remains unclear whether the study of endothelial function provides information that is additive to that of traditional risk factors. METHODS AND RESULTS: Flow-mediated dilation (FMD) and low-flow-mediated constriction (L-FMC) were measured in 451 consecutive patients before coronary angiography. Low-flow-mediated constriction (P< 0.0001) and FMD (P=0.0005) progressively decreased with the number of diseased vessels, and L-FMC showed a significant linear correlation with the SYNTAX score (R=0.38; P< 0.0001). Logistic regression analysis confirmed the association between endothelial function parameters and CAD (P=0.001 for L-FMC, P=0.02 for FMD). Receiver operating characteristic analysis demonstrated that the addition of L-FMC alone and of the combination of FMD and L-FMC improved the predictive power of a model based on traditional risk factors for CAD (area under the curve of the risk factor model=0.716; risk factor model + FMD=0.734, P=0.1 compared with risk factor model; risk factor model + L-FMC=0.771, P=0.004; risk factor model + L-FMC + FMD=0.779, P=0.002). Reclassification statistics showed that the introduction of FMD to the model based on the traditional risk factors correctly reclassified an additional 5% of patients, and that the introduction of L-FMC net correctly reclassified 19% of the patients. There was no correlation between different parameters of endothelial function. CONCLUSION: Endothelial function assessment provides modest but statistically significant additional information in predicting the presence of CAD.

Assessment of sympathetic index from the Valsalva maneuver.

OBJECTIVE: Blood pressure (BP) decline and recovery during the Valsalva maneuver (VM) are used to evaluate the degree of sympathetic failure (SF) but a reliable sympathetic index (SI) derived from VM is lacking. METHODS: Patients with mild (n=20), moderate (n=65), and severe (n=60) SF and 23 healthy controls were evaluated using a standardized battery of autonomic tests. SF was defined as mild (associated with reduced sudomotor volumes at distal leg); moderate (associated with a fall in systolic BP ≥10< 30 mm Hg during the tilt test); and severe (associated with a fall in systolic BP ≥30 mm Hg during the tilt test). Six SIs were compared: SI1 (BP fall during phase 2), SI2 (BP recovery during phase 2), SI3 (the difference in BP between baseline and the end of phase 2), SI4 (the magnitude of phase 4), SI5 (BP recovery time), and SI6 (baroreflex sensitivity index). RESULTS: All indexes showed overall significant differences among tested groups (p<0.05). Only SI3 differentiated all subject groups. Compared to other SIs, SI3 correlated the most with orthostatic hypotension (OH; r=0.62, p < 0.05) during the tilt. CONCLUSIONS: SI3 is the optimal method for calculation of SI since it 1) easily differentiates between healthy controls and those with SF; 2) correlates with the OH, a proxy for a sympathetic failure; 3) tracks the full spectrum of SF (mild-moderate-severe). SI3 expands the utility of quantitative autonomic testing.

Assessment of endothelial function of large, medium, and small vessels: a unified myograph.

Endothelial dysfunction precedes the development of morphological atherosclerotic changes and can also contribute to lesion development in cardiovascular diseases. Currently, there is a lack of a single method to determine endothelial function of the entire range of vessel dimensions from aorta to arterioles. Here we assessed endothelial function of a large range of size arteries using a unified isovolumic myograph method. The method maintains a constant volume of fluid in the lumen of the vessel during contraction and relaxation, which are characterized by an increase and a decrease of pressure, respectively. Segments of six aortas, six common femoral arteries, and six mesenteric arteries from rats; six carotid arteries from mice; and six coronary and carotid arteries from pigs were used. The endothelium-dependent dose-response vasorelaxation was determined with endothelium-dependent vasodilators while arterial preconstriction was induced with vasoconstrictors at a submaximal dose. The circumferential midtension during vascular reactivity varied from 43.1 ± 7.9 to 2.59 ± 0.46 mN/mm (from large to small arteries), whereas the circumferential midstress showed a much smaller variation from 217 ± 23.5 to 123 ± 15.3 kPa (in the same range of vessels). We also found that overinflation and axial overelongation compromised endothelium-dependent vasorelaxation to underscore the significance of vessel preload. In conclusion, an isovolumic myograph was used to unify arterial vasoreactivity from large to small arteries and shows the uniformity of wall stress and %tension throughout the range of vessel sizes.

[Assessment of vascular reactivity by wire myograph]. / Stanovenie cievnej reaktivity pomocou drôtikového myografu.

This paper describes the methodology and application of a wire myograph which has been used for the measurement of vascular reactivity. In an earlier years (pre-1970s) most of the information about the mechanical, morphological and pharmacological properties of vascular smooth muscle was confined only to larger arteries (mainly aorta). Whereas information about smaller arteries was purely inferred from perfusion experiments and histological examination. However, after mid-1970s Prof. Mulvany and Prof. Halpern developed and introduced an astonishing technique, a wire myography, to study the contractile responses of an isolated small resistance arteries (approximately 100-300 microm in internal diameter). This work describes some of the principles used in the investigation of the vessels, based on the use of the small vessel dual wire myograph. A dual myograph allows us simultaneous testing of two vessels. The technique allows segments of small arteries to be mounted as the ring preparations to the myograph chamber, and providing measurements of isometric responses. On the other hand, there are other techniques including an isobaric and isotonic mounting of arteries have been developed to date. The myograph has been used for the investigation of a variety of small and larger arteries and other tubular structures from a wide range of species. In the second part of this report we show an experimental example concerning measurement of endothelial functionality by technique described therein before.

A large animal survival model (Sus scrofa) of extremity ischemia/reperfusion and neuromuscular outcomes assessment: a pilot study.

BACKGROUND: Extremity ischemia/reperfusion has been studied mostly in small-animal models with limited characterization of neuromuscular or functional outcome. The objective of this experiment was to report a large-animal survival model of extremity ischemia/reperfusion using circulating, electromyographic (EMG), gate, and histologic measures of injury and limb recovery. METHODS: Sus scrofa swine (n = 6; mean, 83 kg) were randomized to iliac artery occlusion for 0 (control), 1 (1 HR), 3 (3 HR), or 6 (6 HR) hours. Restoration of flow after a standard large-vessel reconstructive technique (thrombectomy, heparin irrigation, and patch angioplasty) was performed in each of the control, 1HR, 3HR, and 6HR animals, whereas one animal had iliac artery segment excision with no restoration (NR) of axial flow. One animal had operative exposure but no intervention on the iliac artery (sham). Animals were recovered and closely monitored for 2 weeks. Indicators of ischemia/reperfusion and functional recovery, including circulating markers, EMG measures (complex motor action potential), and Tarlov gate scoring (0-4; 0, insensate/paralyzed to 4, normal posture and no gait abnormality) were measured at 24 hours and 72 hours and 7 days and 14 days. Muscle (peroneus) and nerve (peroneal) were collected during necropsy at 14 days to assess gross and histologic changes. Duplex ultrasound was performed serially during the recovery period to confirm patency of vascular reconstruction. RESULTS: There were no deaths or failures of vascular reconstruction. Control had a Tarlov score of 4 and normal EMG measures at each point during recovery (same as sham). Tarlov scores at 1, 3, and 14 days recovery in each of the animals were as follows: 1HR: 3, 3, and 4; 3HR: 1, 2, and 4; 6HR: 1, 2, and 3; and NR: 1, 2, and 4. Complex motor action potential as a percentage of baseline at 1, 2, and 14 days recovery was as follows: 1HR: 56%, 55%, and 84%; 3HR: 9%, 8%, and 57%; 6HR: 5%, 5%, and 16%; and NR: 22%, 28%, and 33%. Muscle and nerve histology was the same in sham, control, and 1HR animals. Moderate degeneration and necrosis was observed in peroneus muscle of the 3HR animals. The peroneal nerve in 3HR demonstrated minimal Wallerian degeneration. Severe necrosis was present, as was minimal regeneration, and peroneal nerve demonstrated moderate Wallerian degeneration in 6HR. CONCLUSION: This study reports a new large-animal survival model of extremity ischemia/reperfusion using circulating, functional, and histologic markers of neuromuscular recovery. Findings provide insight into an extremity ischemic threshold after which functional neuromuscular recovery is lost. Additional study is necessary to define this threshold and factors that may move it to a more or less favorable position in the setting of extremity injury.

Disparity in regional and systemic circulatory capacities: do they affect the regulation of the circulation?

In this review we integrate ideas about regional and systemic circulatory capacities and the balance between skeletal muscle blood flow and cardiac output during heavy exercise in humans. In the first part of the review we discuss issues related to the pumping capacity of the heart and the vasodilator capacity of skeletal muscle. The issue is that skeletal muscle has a vast capacity to vasodilate during exercise [approximately 300 mL (100 g)(-1) min(-1)], but the pumping capacity of the human heart is limited to 20-25 L min(-1) in untrained subjects and approximately 35 L min(-1) in elite endurance athletes. This means that when more than 7-10 kg of muscle is active during heavy exercise, perfusion of the contracting muscles must be limited or mean arterial pressure will fall. In the second part of the review we emphasize that there is an interplay between sympathetic vasoconstriction and metabolic vasodilation that limits blood flow to contracting muscles to maintain mean arterial pressure. Vasoconstriction in larger vessels continues while constriction in smaller vessels is blunted permitting total muscle blood flow to be limited but distributed more optimally. This interplay between sympathetic constriction and metabolic dilation during heavy whole-body exercise is likely responsible for the very high levels of oxygen extraction seen in contracting skeletal muscle. It also explains why infusing vasodilators in the contracting muscles does not increase oxygen uptake in the muscle. Finally, when approximately 80% of cardiac output is directed towards contracting skeletal muscle modest vasoconstriction in the active muscles can evoke marked changes in arterial pressure.

Assessment of vascular function: flow-mediated constriction complements the information of flow-mediated dilatation.

OBJECTIVE: To determine whether vascular function assessed by low-flow-mediated constriction (L-FMC), a novel non-invasive method, complements the information obtained with "traditional" flow-mediated dilatation (FMD). DESIGN AND PATIENTS: In protocol 1, 12 healthy young volunteers underwent FMD and L-FMC measurements at rest and immediately after isometric exercise of the same hand. In protocol 2, 24 patients with coronary artery disease, 24 with congestive heart failure, 24 hypertensive patients and 64 healthy volunteers were enrolled to undergo L-FMC and FMD measurements. RESULTS: In protocol 1, exercise was associated with mean (SD) increases in radial artery blood flow, diameter and L-FMC (from -5.1 (1.5)% to -7.8 (3.4)%, p<0.05), while FMD was significantly blunted (from 6.0 (2.4)% to 3.0 (3.2)%, p<0.05). In protocol 2, both FMD and L-FMC were blunted in the patient groups. Receiver operating curve analysis showed that, as compared with FMD alone, the combination of L-FMC and FMD significantly improved the sensitivity and specificity in detecting patients diagnosed with cardiovascular disease (p<0.05). CONCLUSION: In the first protocol, FMD and L-FMC were shown to be reciprocally regulated. A blunted FMD may, in certain cases, be an expression of increased resting vascular activation and not only of impaired endothelial function. In the second protocol, a statistical approach showed that implementation of L-FMC provides a better characterisation than FMD of vascular function in cardiovascular disease. Vascular (endothelial) function is a complex phenomenon which requires a multifaceted approach; it is suggested that a combination of L-FMC and FMD will provide additive and complementary information to "traditional" FMD measurements.

Vessel calibre and haemoglobin effects on pulse oximetry.

Despite its success as a clinical monitoring tool, pulse oximetry may be improved with respect to the need for empirical calibration and the reports of biases in readings associated with peripheral vasoconstriction and haemoglobin concentration. To effect this improvement, this work aims to improve the understanding of the photoplethysmography signal-as used by pulse oximeters-and investigates the effect of vessel calibre and haemoglobin concentration on pulse oximetry. The digital temperature and the transmission of a wide spectrum of light through the fingers of 57 people with known haemoglobin concentrations were measured and simulations of the transmission of that spectrum of light through finger models were performed. Ratios of pulsatile attenuations of light as used in pulse oximetry were dependent upon peripheral temperature and on blood haemoglobin concentration. In addition, both the simulation and in vivo results showed that the pulsatile attenuation of light through fingers was approximately proportional to the absorption coefficients of blood, only when the absorption coefficients were small. These findings were explained in terms of discrete blood vessels acting as barriers to light transmission through tissue. Due to the influence of discrete blood vessels on light transmission, pulse oximeter outputs tend to be dependent upon haemoglobin concentration and on the calibre of pulsing blood vessels-which are affected by vasoconstriction/vasodilation. The effects of discrete blood vessels may account for part of the difference between the Beer-Lambert pulse oximetry model and empirical calibration.

Monitoring of cardiovascular reactivity to cold stress using digital volume pulse characteristics in health and diabetes.

OBJECTIVE: Cold pressor test (CPT) assesses sympathetic reactivity by the rise in diastolic blood pressure secondary to the vasoconstriction during immersion of hand in cold water. Presently, monitoring of vascular reactivity in health and diabetes during CPT has been attempted by objective measures of Photoplethysmogram (PPG) that include amplitude, upstroke-slope, pulse timings and pulse transit time (PTT). METHODS: Finger-PPG characteristics were studied before and during CPT (1 min) in 11 healthy volunteers and 10 diagnosed Type 2 Diabetes Mellitus (DM) patients. In controls, the recordings were continued for 5 min after CPT. RESULTS: The amplitude of PPG significantly decreased due to cold stress in both control and DM groups (P < 0.0001 and P < 0.003, respectively). However, the decrease in amplitude was significantly lesser (0.42 +/- 0.08 nu vs. 0.25 +/- 0.03 nu, P = 0.04) in DM group than controls. The slope response of PPG resembled the amplitude. PTT was significantly shortened in control and DM groups (180.0 +/- 3.8 ms vs. 187.1 +/- 3.9 ms, P < 0.006, 177.7 +/- 7.0 ms vs. 192.9 +/- 5.6 ms, P = 0.002, respectively) during CPT as compared to baseline. However, the decrease in PTT was significantly higher (-15.2 +/- 3.4 ms vs. -6.0 +/- 1.9 ms, P = 0.03) in DM patients than controls. No significant differences were noticed in Delta changes of peak-to-peak interval, crest time and decay time of PPG between the two groups. CONCLUSION: This preliminary study suggests that the collective responses of PPG amplitude and PTT can be used to objectively quantify the sympathetic reactivity to cold stress in health as well as to detect the deficits of vascular reactivity in diabetes. Further studies would substantiate the simple PPG technique in quantifying the neuronal and vascular dysfunction.

Assessment of renal vasoconstriction in vivo after intra-arterial administration of the isosmotic contrast medium iodixanol compared to the low-osmotic contrast medium iopamidol.

BACKGROUND: Low-osmotic contrast media (LOCM) such as iopamidol are known to increase the renal resistance index (RRI). The aim of our study was to evaluate in vivo the different effects of intra-arterial administration of LOCM in comparison to isosmotic contrast medium (IOCM) such as iodixanol on the human RRI. METHODS: Twenty patients (16 males, 4 females; 66 years on average) with normal renal function (mean creatinine 1.0 mg/dl) had digital subtraction angiography (DSA) of the abdominal and lower-limb arteries. Ten patients received LOCM, and 10 patients IOCM (150 ml on average, 20 ml/s). The RRI was assessed by an experienced nephrologist with duplex ultrasound from 15 min before until 30 min after the first injection with delays of 1-5 min. The basic value of the RRI and differential RRI were calculated. RESULTS: The basic value of the RRI was 0.69 in the LOCM group and 0.71 in the IOCM group. After LOCM a significant increase of the RRI to 0.73 on average (P < or = 0.001) 2 min after the first injection was found, whereas IOCM did not result in a significant change of the RRI (RRI remained 0.71 on average, P > or = 0.1). In the LOCM group, the RRI returned to the basic value after 30 min (+/-2.3 min). CONCLUSIONS: Intra-arterial administration of IOCM had no influence on renal vascular resistance as expressed by the RRI, unlike LOCM, which induced a highly significant increase of the RRI for up to 30 min.

A quantitative assessment of skin blood flow in humans.

Various aspects of skin blood flow (SkBF) in human beings have been studied experimentally for more than seven decades. While reasonably complete phenomenological descriptions of individual factors have emerged from those investigations, little effort has been devoted to assembling the component parts into a coherent description of the entire system. This paper describes an effort to do that. Although the result is essentially a mathematical model of human SkBF, the model is firmly based on empirical data and not merely an abstract theoretical construct. We found that experimental data for human forearm blood flow (FBF) from many sources are well represented by an equation in which the rate of cutaneous blood flow (q (s)) is defined by the equation q (s) = q (s,r) AVD x CVCM x CVCL x CVCE. The coefficient q (s,r) is the perfusion rate at a reference state, and the four component factors are defined as follows: AVD defines centrally mediated active vasodilation as a function of central temperature (T (c)), mean skin temperature (T(s))d intensity of exercise (V(o)(2)) CVCM defines reflexly mediated cutaneous vasoconstriction as a function of (T(s)) CVCL defines locally mediated cutaneous vasoconstriction as a function of local skin temperature (T (s)); and CVCE defines the effect of exercise on cutaneous vasoconstriction and mean arterial pressure. The definition of each component function is based on experimental data. Two conclusions are particularly significant. One is that the study provides a rational explanation, based on the role of (T(s)), for previously disparate opinions about the non-thermal effect of exercise on active cutaneous vasodilation. The other is that it establishes that the four factors combine multiplicatively, and not additively, as previous investigators have suggested.

Hospitalizations with amphetamine abuse among pregnant women.

OBJECTIVE: To examine trends in pregnancy hospitalizations with a diagnosis of amphetamine or cocaine abuse and the prevalence of associated medical complications. METHODS: Data were obtained from the Nationwide Inpatient Sample. Hospitalization ratios per 100 deliveries for amphetamine or cocaine abuse from 1998 to 2004 were tested for linear trends. Amphetamine-abuse hospitalizations were compared with cocaine-abuse hospitalizations and non-substance-abuse hospitalizations. A chi2 analysis was used to compare hospitalization characteristics. Conditional probabilities estimated by logistic regression were used to calculate adjusted prevalence ratios for each medical diagnosis of interest. RESULTS: From 1998 to 2004, the hospitalization ratio for cocaine abuse decreased 44%, whereas the hospitalization ratio for amphetamine abuse doubled. Pregnancy hospitalizations with a diagnosis of amphetamine abuse were geographically concentrated in the West (82%), and were more likely to be among women younger than 24 years than the cocaine-abuse or non-substance-abuse hospitalizations. Most medical conditions were more prevalent in the amphetamine-abuse group than the non-substance-abuse group. When the substance abuse groups were compared with each other, obstetric diagnoses associated with infant morbidity such as premature delivery and poor fetal growth were more common in the cocaine-abuse group, whereas vasoconstrictive effects such as cardiovascular disorders and hypertension complicating pregnancy were more common in the amphetamine-abuse group. CONCLUSION: As pregnancy hospitalizations with a diagnosis of amphetamine abuse continue to increase, clinicians should familiarize themselves with the adverse consequences of amphetamine abuse during pregnancy and evidence-based guidelines to deal with this high-risk population. LEVEL OF EVIDENCE: III.

High-resolution transthoracic echocardiography of the left anterior descending coronary artery: a novel noninvasive assessment of coronary vasoreactivity.

OBJECTIVES: The study objective was to determine the effects of salbutamol and nitroglycerin (NTG) on the luminal diameter of the left anterior descending (LAD) coronary artery, as measured noninvasively by the novel technique of high-resolution transthoracic echocardiography (HRTTE). BACKGROUND: Invasive studies of the coronary arteries have demonstrated vasodilatation by salbutamol and NTG. By using a novel technique of HRTTE, combined with assessment of augmentation index (AIx, a marker of peripheral arterial stiffness) by means of applanation tonometry from the radial artery (pulse wave analysis), we studied the vasomotion of the proximal LAD in healthy volunteers. METHODS: Nineteen male subjects (age 31 +/- 5 years, mean +/- standard deviation) underwent HRTTE measurement of the wall thickness, luminal diameter, and external diameter of the proximal LAD, and AIx at baseline and 5, 10, 15, and 20 minutes after administration of inhaled salbutamol (400 microg) and, after return to baseline, sublingual NTG (300 microg). RESULTS: Salbutamol induced a 44% +/- 28% increase in LAD luminal diameter (2.8 +/- 0.8 mm to 3.7 +/- 0.9 mm, P < .001) and a reduction in AIx (-13.4% +/- 6.6%, P < .001). NTG induced greater changes in both parameters (60% +/- 30% increase in luminal diameter from baseline, 2.7 +/- 0.9 mm to 4.4 +/- 1.1 mm, P < .001; and reduction in AIx -24.1% +/- 8.2%, P < .001). Changes in LAD diameter and AIx were related after both salbutamol (r = -0.53, P = .02) and NTG (r = -0.57, P = .01). No significant change was detected in wall thickness. CONCLUSION: HRTTE is able to detect the LAD coronary artery vasodilating effects of NTG and salbutamol and correlates with peripheral vascular reactivity to these vasodilators. This approach provides a useful tool for the noninvasive assessment of coronary vasoreactivity.