["The Journal of Physiology, Volume 604, Issue 13, Page 5296-5315, 1 July 2026. ", "\nAbstract Figure Legend: Cardiac function in micro‐gravity and hyper‐gravity environments is still under investigation and restricted to a limited number of cardiac parameters. This study proposes to assess the cardiac function from micro‐ (0g) to hyper‐gravity (3g) conditions through a multiscale modelling approach. The model has been validated using experimental data from literature (human centrifuge and parabolic flight studies). The model provides an in‐depth description of the cardiac behaviour, revealing: (i) distinct responses between left and right heart haemodynamics (as shown by the left and right ventricular PV loops); (ii) enhanced cardiac efficiency and performance in micro‐gravity; (iii) reduced cardiac efficiency along with impaired energy supply/demand ratio both at the heart and coronary levels in hyper‐gravity.\n\n\n\n\n\n\n\n\n\nAbstract\nGravity changes with respect to the 1g terrestrial condition induce several cardiovascular alterations, from fluid shift and blood volume reduction to orthostatic hypotension and venous pooling. Micro‐gravity and hyper‐gravity exposure characterizes space missions and aeronautical flights, as well as terrestrial analogues such as centrifuges, bed rest studies, and parabolic flights. Despite a growing number of clinical measures becoming available, cardiac function in these extreme conditions is still incomplete and difficult to obtain. Thus, computational haemodynamics provides a powerful and reliable tool to understand the cardiac response. We propose a 0D‐1D multiscale cardiovascular model to investigate the steady‐state acute cardiac response to gravity changes (from 0g to 3g). The model combines a 1D description of the coronary circulation and arterial tree, with a 0D parameterization of the peripheral microcirculation, the venous return, the cardiopulmonary and the cerebrovascular‐ocular circulations. The overall model is equipped with short‐term regulation mechanisms, and accounts for gravity and posture changes. After a thorough validation using measured data from literature involving the most common central haemodynamic parameters (i.e. HR, MAP, SV and CO), the model provides an in‐depth description of the cardiac response from micro‐ (0g) to hyper‐gravity (3g), highlighting: (i) a different behaviour between left and right heart haemodynamics; (ii) an improvement in cardiac efficiency and cardiac performance in micro‐gravity; (iii) a worsening of cardiac efficiency and an energy supply/demand impairment both at heart and coronary levels in hyper‐gravity. Therefore, the modelling approach proves to be an important tool in shedding light on space medicine.\n\n\n\n\n\n\n\n\n\nKey points\n\nGravity changes from micro‐ to hyper‐gravity induce several cardiovascular alterations, from fluid shift and blood volume reduction to orthostatic hypotension and venous pooling.\nAlthough the overall cardiovascular response is clear, details of the cardiac function in these extreme conditions are still incomplete and difficult to obtain.\nWe propose a validated multiscale cardiovascular model to investigate the steady‐state acute cardiac response to gravity changes (from 0g to 3g).\nAfter a thorough validation against the most common central haemodynamic parameters in literature, present results show: (i) a different behaviour between left and right heart haemodynamics; (ii) an improvement of cardiac efficiency and cardiac performance in micro‐gravity; (iii) an energy supply/demand impairment in hyper‐gravity.\nThe computational approach is a useful and reliable tool in exploring the response of cardiac parameters which are difficult to investigate experimentally, aiming to shed light on the cardiac function under altered gravitational force.\n\n\n"]