What Is the Heart? Anatomy, Function, Pathophysiology, and Misconceptions.

Cardiac dynamics are traditionally linked to a left ventricle, right ventricle, and septum morphology, a topography that differs from the heart's five-century-old anatomic description of containing a helix and circumferential wrap architectural configuration. Torrent Guasp's helical ventricular myocardial band (HVMB) defines this anatomy and its structure, and explains why the heart's six dynamic actions of narrowing, shortening, lengthening, widening, twisting, and uncoiling happen. The described structural findings will raise questions about deductions guiding "accepted cardiac mechanics", and their functional aspects will challenge and overturn them. These suppositions include the LV, RV, and septum description, timing of mitral valve opening, isovolumic relaxation period, reasons for torsion/twisting, untwisting, reasons for longitudinal and circumferential strain, echocardiographic sub segmentation, resynchronization, RV function dynamics, diastolic dysfunction's cause, and unrecognized septum impairment. Torrent Guasp's revolutionary contributions may alter future understanding of the diagnosis and treatment of cardiac disease.

Mitral regurgitation: anatomy is destiny.

Mitral regurgitation (MR) occurs when any of the valve and ventricular mitral apparatus components are disturbed. As MR progresses, left ventricular remodelling occurs, ultimately causing heart failure when the enlarging left ventricle (LV) loses its conical shape and becomes globular. Heart failure and lethal ventricular arrhythmias may develop if the left ventricular end-systolic volume index exceeds 55 ml/m2. These adverse changes persist despite satisfactory correction of the annular component of MR. Our goal was to describe this process and summarize evolving interventions that reduce the volume of the left ventricle and rebuild its elliptical shape. This 'valve/ventricle' approach addresses the spherical ventricular culprit and offsets the limits of treating MR by correcting only its annular component.

Effects of antegrade versus integrated blood cardioplegia on left ventricular function evaluated by echocardiographic real-time 3-dimensional speckle tracking.

OBJECTIVE: The objective of this study was to evaluate left ventricular free wall and interventricular septal function by 2-dimensional transthoracic echocardiography and live/real-time 3-dimensional transthoracic speckle tracking echocardiography before and after on-pump cardiac surgery and to assess the effect of mode of cardioplegia delivery. METHODS: A total of 22 patients were studied 1 day before and 4 to 5 days after surgery. Cold blood cardioplegia was delivered by intermittent antegrade infusion or by the integrated method. The latter includes a combination of intermittent antegrade and retrograde cardioplegia with a terminal warm amino acid-enriched reperfusion. RESULTS: The overall group displayed significant deterioration of septal function after surgery by 2-dimensional transthoracic echocardiography, as assessed by wall motion score index, yet subgroup analysis by 3-dimensional transthoracic speckle tracking echocardiography permitted distinction of outcomes achieved by antegrade or integrated delivery methods. Analysis after surgery showed that only the antegrade group displayed statistically significant deterioration in the strain parameters of some of the segments of the septum and free wall when strain was measured in the free wall and septum in the longitudinal, circumferential, and radial modes of deformation (P < .05). In contrast, only the integrated group displayed significant improvement in global radial, circumferential, and longitudinal strain (P < .05). CONCLUSIONS: These findings by 3-dimensional transthoracic speckle tracking echocardiography indicate that integrated cardioplegia offers superior myocardial protection of the left ventricular free wall and septum compared with the antegrade mode of cardioplegia delivery.

Ventricular structure-function relations in health and disease: part II. Clinical considerations.

Normal cardiac function of the left and right ventricles, together with the septum, is related to form/function interactions within the helical ventricular myocardial band. This knowledge is a prerequisite to understanding form/function interactions in diseases and for planning new treatments. Topics discussed include congestive heart failure in dilated hearts of ischaemic, valvar or nonischaemic origin as well as diastolic dysfunction. Similar thinking underlies novel treatments for dyssynchrony in pacing, together with focusing upon varying global left or right ventricular anatomy to correct mitral and tricuspid insufficiency caused by tethering of the leaflets. The septum is the lion of the right ventricle and insight is provided into offsetting septal damage during cardiac surgery, rebuilding its anatomical structure in post-tetralogy pulmonary insufficiency, as well as rectifying its dysfunction by decompression in patients with a left ventricular assist device.

Ventricular structure-function relations in health and disease: Part I. The normal heart.

The heart's structure-function relationships explain normal cardiac dynamics and clarify how they are disrupted by disease. For 500 years, anatomists described circumferential and helical cardiac fibres, yet disagreed about their relationships. One current model is attributed to Torrent Guasp who described functional pathways, the helical ventricular myocardial band (HVMB) with two interconnected loops: an outer basal loop with transverse fibres surrounds an inner apical helical loop that is composed of oblique descending and ascending segments that create a conical apical vortex. This review addresses the potential role of the HVMB in explaining the mechanics of isovolumic contraction, ejection, post-ejection isovolumic interval, rapid filling, torsion and recoiling. During the post-ejection isovolumic interval, a ∼ 90-ms hiatus exists between the end of contraction of the descending and the ascending segments. Compromise of this hiatus by disease disturbs the interdependence between torsion and 'untwisting' and impairs cardiac function. The validity of conventional expressions such as isovolumic relaxation, hyperechogenic septal line, untwisting and mitral valve opening will be revisited.

Studies of isolated global brain ischaemia: I. Overview of irreversible brain injury and evolution of a new concept - redefining the time of brain death.

Despite advanced cardiac life support (ACLS), the mortality from sudden death after cardiac arrest is 85-95%, and becomes nearly 100% if ischaemia is prolonged, as occurs following unwitnessed arrest. Moreover, 33-50% of survivors following ACLS after witnessed arrest develop significant neurological dysfunction, and this rises to nearly 100% in the rare survivors of unwitnessed arrest. Although, whole body (cardiac) survival improves to 30% following recent use of emergency cardiopulmonary bypass, sustained neurological dysfunction remains a devastating and unresolved problem. Our studies suggest that both brain and whole body damage reflect an ischaemic/reperfusion injury that follows the present reperfusion methods that use normal blood, which we term 'uncontrolled reperfusion'. In contrast, we have previously introduced the term 'controlled reperfusion', which denotes controlling both the conditions (pressure, flow and temperature) as well as the composition (solution) of the reperfusate. Following prolonged ischaemia of the heart, lung and lower extremity, controlled reperfusion resulted in tissue recovery after ischaemic intervals previously thought to produce irreversible cellular injury. These observations underlie the current hypothesis that controlled reperfusion will become an effective treatment of the otherwise lethal injury of prolonged brain ischaemia, such as with unwitnessed arrest, and we tested this after 30 min of normothermic global brain ischaemia. This review, and the subsequent three studies will describe the evolution of the concept that controlled reperfusion will restore neurological function to the brain following prolonged (30 min) ischaemia. To provide a familiarity and rationale for these studies, this overview reviews the background and current treatment of sudden death, the concepts of controlled reperfusion, recent studies in the brain during whole body ischaemia, and then summarizes the three papers in this series on a new brain ischaemia model that endorses our hypothesis that controlled reperfusion allows complete neurological recovery following 30 min of normothermic global brain ischaemia. These findings may introduce innovative management approaches for sudden death, and perhaps stroke, because the brain is completely salvageable following ischaemic times thought previously to produce infarction.

Studies of isolated global brain ischaemia: II. Controlled reperfusion provides complete neurologic recovery following 30 min of warm ischaemia - the importance of perfusion pressure.

OBJECTIVES: Neurologic injury after sudden death is likely due to a reperfusion injury following prolonged brain ischaemia, and remains problematic, especially if the cardiac arrest is unwitnessed. This study applies a newly developed isolated model of global brain ischaemia (simulating unwitnessed sudden death) for 30 min to determine if controlled reperfusion permits neurologic recovery. METHODS: Among the 17 pigs undergoing 30 min of normothermic global brain ischaemia, 6 received uncontrolled reperfusion with regular blood (n = 6), and 11 were reperfused for 20 min with a warm controlled blood reperfusate containing hypocalcaemia, hyper-magnesemia, alkalosis, hyperosmolarty and other constituents that were passed through a white blood cell filter and delivered at flow rates of 350 cc/min (n = 3), 550 cc/min (n = 2) or 750 cc/min (n = 6). Neurologic deficit score (NDS) evaluated brain function (score 0 = normal, 500 = brain death) 24 h post-reperfusion and 2,3,5-triphenyltetrazolium chloride (TTC) staining determined brain infarction. RESULTS: Regular blood (uncontrolled) reperfusion caused negligible brain O(2) uptake by IN Vivo Optical Spectroscopy (INVOS) (<10-15% O(2) extraction), oxidant damage demonstrated by raised conjugated diene (CD) levels (1.78 ± 0.13 A233 mn), multiple seizures, 1 early death from brain herniation, high NDS (249 ± 39) in survivors, brain oedema (84.4 ± 0.6%) and extensive cerebral infarctions. Conversely, controlled reperfusion restored surface brain oxygen saturation by INVOS to normal (55-70%), but the extent of neurologic recovery was determined by the brain reperfusion pressure. Low pressure reperfusion (independent of flow) produced the same adverse functional, metabolic and anatomic changes that followed uncontrolled reperfusion in seven pigs (three at 350 cc/min, two at 550 and two at 750 cc/min). Conversely, higher reperfusion pressure in four pigs (all at 750 cc/min) resulted in NDS of 0-70* indicating complete (n = 2) or near complete (n = 2) neurological recovery, negligible CDs production (1.29 ± 0.06 A233mn)*, minimal brain oedema (80.6 ± 0.2%)* and no infarction by TTC stain. CONCLUSIONS: Brain injury can be avoided after 30 min of normothermic cerebral ischaemia if controlled reperfusion pressure is >50 mmHg, but the lower pressure (<50 mmHg) controlled reperfusion that is useful in other organs cannot be transferred to the brain. Moreover, INVOS is a poor guide to the adequacy of cerebral perfusion and the capacity of controlled brain reperfusion to restore neurological recovery. *P < 0.001 versus uncontrolled or low pressure controlled reperfusion.

Studies of isolated global brain ischaemia: III. Influence of pulsatile flow during cerebral perfusion and its link to consistent full neurological recovery with controlled reperfusion following 30 min of global brain ischaemia.

OBJECTIVE: Brain damage is universal in the rare survivor of unwitnessed cardiac arrest. Non-pulsatile-controlled cerebral reperfusion offsets this damage, but may simultaneously cause brain oedema when delivered at the required the high mean perfusion pressure. This study analyses pulsatile perfusion first in control pigs and then using controlled reperfusion after prolonged normothermic brain ischaemia (simulating unwitnessed arrest) to determine if it might provide a better method of delivery for brain reperfusion. METHODS: Initial baseline studies during isolated brain perfusion in 12 pigs (six non-pulsatile and six pulsatile) examined high (750 cc/min) then low (450 cc/min) fixed flow before and after transient (30 s) ischaemia, while measuring brain vascular resistance and oxygen metabolism. Twelve subsequent pigs underwent 30 min of normothermic global brain ischaemia followed by either uncontrolled reperfusion with regular blood (n = 6) or pulsatile-controlled reperfusion (n = 6) before unclamping brain inflow vessels. Functional neurological deficit score (NDS; score: 0, normal; 500, brain death) was evaluated 24 h post-reperfusion. RESULTS: High baseline flow rates with pulsatile and non-pulsatile perfusion before and after transient ischaemia maintained normal arterial pressures (90-100 mmHg), surface oxygen levels IN Vivo Optical Spectroscopy (INVOS) and oxygen uptake. In contrast, oxygen uptake fell after 30 s ischaemia at 450 cc/min non-pulsatile flow, but improved following pulsatile perfusion, despite its delivery at lower mean cerebral pressure. Uncontrolled (normal blood) reperfusion after 30 min of prolonged ischaemia, caused negligible INVOS O(2) uptake (<10-15%), raised conjugated dienes (CD; 1.75 ± 0.15 A(233 mn)), one early death, multiple seizures, high NDS (243 ± 16) and extensive cerebral infarcts (2,3,5-triphenyl tetrazolium chloride stain) and oedema (84.1 ± 0.6%). Conversely, pulsatile-controlled reperfusion pigs exhibited normal O(2) uptake, low CD levels (1.31 ± 0.07 A(233 mn); P < 0.01 versus uncontrolled reperfusion), no seizures and a low NDS (32 ± 14; P < 0.001 versus uncontrolled reperfusion); three showed complete recovery (NDS = 0) and all could sit and eat. Post-mortem brain oedema was minimal (81.1 ± 0.5; P < 0.001 versus uncontrolled reperfusion) and no infarctions occurred. CONCLUSIONS: Pulsatile perfusion lowers cerebral vascular resistance and improves global O(2) uptake to potentially offset post-ischaemic oedema following high-pressure reperfusion. The irreversible functional and anatomic damage that followed uncontrolled reperfusion after a 30-min warm global brain ischaemia interval was reversed by pulsatile-controlled reperfusion, as its delivery resulted in consistent near complete neurological recovery and absent brain infarction.

Studies of isolated global brain ischaemia: I. A new large animal model of global brain ischaemia and its baseline perfusion studies.

OBJECTIVES: Neurological injury after global brain ischaemia (i.e. sudden death) remains problematic, despite improving cardiac survival. Unfortunately, sudden death models introduce unwanted variables for studying the brain because of multiple organ injury. To circumvent this, a new minimally invasive large animal model of isolated global brain ischaemia, together with baseline perfusion studies is described. METHODS: The model employs neck and small (3-4 inches) supra-sternal incisions to block inflow from carotid and vertebral arteries for 30 min of normothermic ischaemia. Neurological changes after 24 h in six pigs was compared with six Sham pigs assessing neurological deficit score (NDS, 0 = normal, 500 = brain death), brain oedema and cerebral infarction by 2,3,5-triphenyltetrazolium chloride (TTC) stain. Six other pigs had baseline perfusion characteristics in this new model evaluated at carotid flows of 750, 550 and 450 cc/min, with cerebral perfusion pressure, cerebral oximeter saturation [IN Vivo Optical Spectroscopy (INVOS)] and transcranial O(2) uptake measurements. RESULTS: The model never altered cardiac or pulmonary function, and six Sham pigs had normal (NDS = 0) neurological recovery without brain injury. Conversely, 24 h analysis showed that 30 min of global normothermic brain ischaemia caused multiple post-reperfusion seizures (P < 0.001 versus Sham), raised NDS (231 ± 16; P < 0.001 versus Sham) in four of six survivors and caused marked post-brain oedema (P < 0.001 versus Sham) and extensive cerebral infarctions (TTC stain; P < 0.001 versus Sham). Baseline perfusion showed 750 cc/min flow rate produced normal INVOS levels and O(2) consumption at mean 90-100 mmHg carotid pressure. Carotid pressure and INVOS fell at mid- and low-flow rates. Although INVOS did not change, 450 cc/min flow lowered global O(2) consumption, which further decreased after transient ischaemia (30 s) and 5 min of reperfusion. CONCLUSIONS: This new isolated global brain model consistently caused anatomic, biochemical and functional neurological damage in pigs after 30 min of ischaemia. Flows of 750 cc/min maintained normal mean systemic arterial (90-100 mmHg) pressure, INVOS levels and O(2) consumption. Cerebral pressure and INVOS fell in mid- and low-flow studies. A disparity existed between INVOS oxygen saturation and global O(2) consumption at lower flow rates of 450 cc/min following transient ischaemia, indicating that surface oxygen saturation measurement does not reflect global brain O(2) consumption.

Resuscitation after prolonged cardiac arrest: effects of cardiopulmonary bypass and sodium-hydrogen exchange inhibition on myocardial and neurological recovery.

OBJECTIVE: To determine if cardiopulmonary bypass (CPB), together with inhibition of the sodium-hydrogen exchanger (NHE), limits myocardial and neurological injury and improves recovery after prolonged (unwitnessed) cardiac arrest (CA), as NHE inhibition improved recovery after deep hypothermic circulatory arrest. METHODS: Twenty-seven pigs (31-39 kg) underwent 15 min of prolonged (no-flow) CA followed by 10 min of cardiopulmonary resuscitation-advanced life support (CPR-ALS). Subjects with restoration of spontaneous circulation (ROSC) during CPR-ALS received either no drug (n=6) or an inhibitor of the NHE (HOE-642; n=5). In the 16 unsuccessfully resuscitated animals, peripheral normothermic CPB was instituted, and either no drug (n=9) or similar HOE-642 (n=7) therapy started. Hemodynamic data, a species-specific neurological deficit score (0=normal to 500=brain death), and mortality were recorded at 24h, and biochemical variables of organ injury measured. RESULTS: CPR-ALS restored ROSC in 41% (11/27) of animals, but was unsuccessful in 59% (16/27) that required CPB. Without CPB, HOE-642 increased cardiac index and decreased vascular resistance; with CPB, HOE-642 caused higher pump flows (3.4±0.6 l min(-1)m(-2) vs 2.5±0.7 l min(-1)m(-2); p<0.001) and higher post-arrest cardiac index; but animals required more vasopressors (p=0.019) from drug-induced vasodilation. No differences between biochemical markers of oxidative and organ injury and overall 24-h mortality (20%) were found between groups. Neurological score was improved at 24h compared with 4h only after HOE-642 treatment with (150±34 vs 220±43; p=0.003) or without CPB (162±39 vs 238±48; p≤0.001), but failed to reach statistical difference with respect to the untreated group. CONCLUSIONS: CPB is an effective resuscitative tool to treat prolonged CA but there is limited improvement of neurological function. NHE inhibition augments cardiac and neurological function, but its effect was less pronounced than in other studies.